Macrocyclization strategies for cyclic peptides and peptidomimetics

Clément Bechtler and Christina Lamers

RSC Med. Chem., 2021, 12, 1325
DOI: 10.1039/D1MD00083G

Diarylethene moiety as an enthalpy-entropy switch: photoisomerizable stapled peptides for modulating p53/MDM2 interaction

Alexander V. Strizhak, Oleg Babii, Sergii Afonin, Iuliia Bakanovich, Teodors Pantelejevs, Wenshu Xu, Elaine Fowler, Rohan Eapen, Krishna Sharma, Maxim O. Platonov, Vasyl V. Hurmach, Laura Itzhaki, Marko Hyvönen, Anne S. Ulrich, David R. Spring and Igor V. Komarov

Org. Biomol. Chem., 2020, 18, 5359
DOI: 10.1039/D0OB00831A

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer

Sooho Ko, Joo-Young Kim, Jung Yeon Park, You-jin Jung, Min-Jae Choi, Kyeong Sik Jin, Yongju Kim, Yong-beom Lim and Woo-jin Jeong

Chem. Sci., 2023, 14, 9600
DOI: 10.1039/D3SC03758D

Stereoisomerism of stapled peptide inhibitors of the p53-Mdm2 interaction: an assessment of synthetic strategies and activity profiles

Tsz Ying Yuen, Christopher J. Brown, Yuezhen Xue, Yaw Sing Tan, Fernando J. Ferrer Gago, Xue Er Lee, Jin Yong Neo, Dawn Thean, Hung Yi Kristal Kaan, Anthony W. Partridge, Chandra S. Verma, David P. Lane and Charles W. Johannes

Chem. Sci., 2019, 10, 6457
DOI: 10.1039/C9SC01456J

Phage-displayed macrocyclic glycopeptide libraries

Simon Ng and Ratmir Derda

Org. Biomol. Chem., 2016, 14, 5539
DOI: 10.1039/C5OB02646F

Triazole-stapled p53 mimetics as MDM2 inhibitors: structural and thermodynamic origin of enhanced binding affinity

Vikram Gaikwad, Pushyaraga P. Venugopal and Rajarshi Chakrabarti

Phys. Chem. Chem. Phys., 2026, 28, 6353
DOI: 10.1039/D5CP03813H

Macrocyclisation and functionalisation of unprotected peptides via divinyltriazine cysteine stapling

Naomi S. Robertson, Stephen J. Walsh, Elaine Fowler, Masao Yoshida, Sam M. Rowe, Yuteng Wu, Hannah F. Sore, Jeremy S. Parker and David R. Spring

Chem. Commun., 2019, 55, 9499
DOI: 10.1039/C9CC05042F

Targeted covalent inhibitors of MDM2 using electrophile-bearing stapled peptides

Jiraborrirak Charoenpattarapreeda, Yaw Sing Tan, Jessica Iegre, Stephen J. Walsh, Elaine Fowler, Rohan S. Eapen, Yuteng Wu, Hannah F. Sore, Chandra S. Verma, Laura Itzhaki and David R. Spring

Chem. Commun., 2019, 55, 7914
DOI: 10.1039/C9CC04022F

A highly sensitive fluorescent light-up probe for real-time detection of the endogenous protein target and its antagonism in live cells

Junlong Geng, Walter L. Goh, Chongjing Zhang, David P. Lane, Bin Liu, Farid Ghadessy and Yen Nee Tan

J. Mater. Chem. B, 2015, 3, 5933
DOI: 10.1039/C5TB00819K

Investigating peptide sequence variations for ‘double-click’ stapled p53 peptides

Yu Heng Lau, Peterson de Andrade, Niklas Sköld, Grahame J. McKenzie, Ashok R. Venkitaraman, Chandra Verma, David P. Lane and David R. Spring

Org. Biomol. Chem., 2014, 12, 4074
DOI: 10.1039/C4OB00742E

Enhancing the gastrointestinal stability of salmon calcitonin through peptide stapling

Hiba Ghareeb and Norman Metanis

Chem. Commun., 2023, 59, 6682
DOI: 10.1039/D3CC01140B

Receptor-templated stapling of intrinsically disordered peptide ligands

Conor M. Haney and W. Seth Horne

Org. Biomol. Chem., 2015, 13, 4183
DOI: 10.1039/C5OB00269A

Peptide stapling techniques based on different macrocyclisation chemistries

Yu Heng Lau, Peterson de Andrade, Yuteng Wu and David R. Spring

Chem. Soc. Rev., 2015, 44, 91
DOI: 10.1039/C4CS00246F

Stabilization of peptides against proteolysis through disulfide-bridged conjugation with synthetic aromatics

Yaqi Chen, Tao Li, Jianguo Li, Shiyan Cheng, Jinghui Wang, Chandra Verma, Yibing Zhao and Chuanliu Wu

Org. Biomol. Chem., 2017, 15, 1921
DOI: 10.1039/C6OB02786E

Ketoxime peptide ligations: oxidative couplings of alkoxyamines to N-aryl peptides

Quibria A. E. Guthrie, Hailey A. Young and Caroline Proulx

Chem. Sci., 2019, 10, 9506
DOI: 10.1039/C9SC04028E

Modulating protein–protein interactions: the potential of peptides

Laura Nevola and Ernest Giralt

Chem. Commun., 2015, 51, 3302
DOI: 10.1039/C4CC08565E

Copper–ligand clusters dictate size of cyclized peptide formed during alkyne–azide cycloaddition on solid support

Rene Kandler, Samir Das and Arundhati Nag

RSC Adv., 2021, 11, 4842
DOI: 10.1039/D0RA07491H

Efficient development of stable and highly functionalised peptides targeting the CK2α/CK2β protein–protein interaction

Jessica Iegre, Paul Brear, David J. Baker, Yaw Sing Tan, Eleanor L. Atkinson, Hannah F. Sore, Daniel H. O' Donovan, Chandra S. Verma, Marko Hyvönen and David R. Spring

Chem. Sci., 2019, 10, 5056
DOI: 10.1039/C9SC00798A

Accessing diverse bicyclic peptide conformations using 1,2,3-TBMB as a linker

Haritha Krishna Sudhakar, Jackie Tsz Ki Yau, Lisa J. Alcock and Yu Heng Lau

Org. Biomol. Chem., 2024, 22, 6095
DOI: 10.1039/D4OB00901K

Water-soluble, stable and azide-reactive strained dialkynes for biocompatible double strain-promoted click chemistry

Krishna Sharma, Alexander V. Strizhak, Elaine Fowler, Xuelu Wang, Wenshu Xu, Claus Hatt Jensen, Yuteng Wu, Hannah F. Sore, Yu Heng Lau, Marko Hyvönen, Laura S. Itzhaki and David R. Spring

Org. Biomol. Chem., 2019, 17, 8014
DOI: 10.1039/C9OB01745C

Recent advances in peptide macrocyclization strategies

Pengyuan Fang, Wing-Ka Pang, Shouhu Xuan, Wai-Lun Chan and Ken Cham-Fai Leung

Chem. Soc. Rev., 2024, 53, 11725
DOI: 10.1039/D3CS01066J

Peptide-based inhibitors of protein–protein interactions: biophysical, structural and cellular consequences of introducing a constraint

Hongshuang Wang, Robert S. Dawber, Peiyu Zhang, Martin Walko, Andrew J. Wilson and Xiaohui Wang

Chem. Sci., 2021, 12, 5977
DOI: 10.1039/D1SC00165E

Photo-induced radical thiol–ene chemistry: a versatile toolbox for peptide-based drug design

Marzieh Ahangarpour, Iman Kavianinia, Paul W. R. Harris and Margaret A. Brimble

Chem. Soc. Rev., 2021, 50, 898
DOI: 10.1039/D0CS00354A

Stapling of unprotected helical peptides via photo-induced intramolecular thiol–yne hydrothiolation

Yuan Tian, Jingxu Li, Hui Zhao, Xiangze Zeng, Dongyuan Wang, Qisong Liu, Xiaogang Niu, Xuhui Huang, Naihan Xu and Zigang Li

Chem. Sci., 2016, 7, 3325
DOI: 10.1039/C6SC00106H

Divergent unprotected peptide macrocyclisation by palladium-mediated cysteine arylation

Anthony J. Rojas, Chi Zhang, Ekaterina V. Vinogradova, Nathan H. Buchwald, John Reilly, Bradley L. Pentelute and Stephen L. Buchwald

Chem. Sci., 2017, 8, 4257
DOI: 10.1039/C6SC05454D

Landscaping macrocyclic peptides: stapling hDM2-binding peptides for helicity, protein affinity, proteolytic stability and cell uptake

Aline D. de Araujo, Junxian Lim, Kai-Chen Wu, Huy N. Hoang, Huy T. Nguyen and David P. Fairlie

RSC Chem. Biol., 2022, 3, 895
DOI: 10.1039/D1CB00231G

Stapling strategy enables improvement of antitumor activity and proteolytic stability of host-defense peptide hymenochirin-1B

Yulei Li, Minghao Wu, Qi Chang and Xia Zhao

RSC Adv., 2018, 8, 22268
DOI: 10.1039/C8RA03446J

A proline-derived transannular N-cap for nucleation of short α-helical peptides

Yuan Tian, Dongyuan Wang, Jingxu Li, Chuan Shi, Hui Zhao, Xiaogang Niu and Zigang Li

Chem. Commun., 2016, 52, 9275
DOI: 10.1039/C6CC04672J

Peptide macrocyclization by transition metal catalysis

Daniel G. Rivera, Gerardo M. Ojeda-Carralero, Leslie Reguera and Erik V. Van der Eycken

Chem. Soc. Rev., 2020, 49, 2039
DOI: 10.1039/C9CS00366E

An in-tether chiral center modulates the proapoptotic activity of the KLA peptide

Jingxu Li, Kuan Hu, Hailing Chen, YuJie Wu, Longjian Chen, Feng Yin, Yuan Tian and Zigang Li

Chem. Commun., 2017, 53, 10452
DOI: 10.1039/C7CC04923D

Polyfluorinated reagents for peptide stapling

Wanzhen Lin, Xin Ding, Jun-Wei Han, Li-Shuang Yu and Fa-Jie Chen

Org. Chem. Front., 2025, 12, 2777
DOI: 10.1039/D5QO00112A

Improving cell penetration of helical peptides stabilized by N-terminal crosslinked aspartic acids

Hui Zhao, Yanhong Jiang, Yuan Tian, Dan Yang, Xuan Qin and Zigang Li

Org. Biomol. Chem., 2017, 15, 459
DOI: 10.1039/C6OB02501C

Switching substitution groups on the in-tether chiral centre influences backbone peptides’ permeability and target binding affinity

Yixiang Jiang, Kuan Hu, Xiaodong Shi, Qingzhuang Tang, ZiChen Wang, Xiyang Ye and Zigang Li

Org. Biomol. Chem., 2017, 15, 541
DOI: 10.1039/C6OB02289H

Stapled peptides as a new technology to investigate protein–protein interactions in human platelets

Jessica Iegre, Niaz S. Ahmed, Josephine S. Gaynord, Yuteng Wu, Kara M. Herlihy, Yaw Sing Tan, Maria E. Lopes-Pires, Rupam Jha, Yu Heng Lau, Hannah F. Sore, Chandra Verma, Daniel H. O' Donovan, Nicholas Pugh and David R. Spring

Chem. Sci., 2018, 9, 4638
DOI: 10.1039/C8SC00284C

Reversible stapling of unprotected peptides via chemoselective methionine bis-alkylation/dealkylation

Xiaodong Shi, Rongtong Zhao, Yixiang Jiang, Hui Zhao, Yuan Tian, Yanhong Jiang, Jingxu Li, Weirong Qin, Feng Yin and Zigang Li

Chem. Sci., 2018, 9, 3227
DOI: 10.1039/C7SC05109C

Red-light modulated ortho-chloro azobenzene photoswitch for peptide stapling via aromatic substitution

Mia Kapun, F. Javier Pérez-Areales, Nicola Ashman, Pamela J. E. Rowling, Tim Schober, Elaine Fowler, Laura S. Itzhaki and David R. Spring

RSC Chem. Biol., 2024, 5, 49
DOI: 10.1039/D3CB00176H

Peptide macrocyclisation via intramolecular interception of visible-light-mediated desulfurisation

Frances R. Smith, Declan Meehan, Rhys C. Griffiths, Harriet J. Knowles, Peiyu Zhang, Huw E. L. Williams, Andrew J. Wilson and Nicholas J. Mitchell

Chem. Sci., 2024, 15, 9612
DOI: 10.1039/D3SC05865D

Advances on chemically modified antimicrobial peptides for generating peptide antibiotics

Samilla B. Rezende, Karen G. N. Oshiro, Nelson G. O. Júnior, Octávio L. Franco and Marlon H. Cardoso

Chem. Commun., 2021, 57, 11578
DOI: 10.1039/D1CC03793E

Double quick, double click reversible peptide “stapling”

Claire M. Grison, George M. Burslem, Jennifer A. Miles, Ludwig K. A. Pilsl, David J. Yeo, Zeynab Imani, Stuart L. Warriner, Michael E. Webb and Andrew J. Wilson

Chem. Sci., 2017, 8, 5166
DOI: 10.1039/C7SC01342F

Hydrocarbon constrained peptides – understanding preorganisation and binding affinity

Jennifer A. Miles, David J. Yeo, Philip Rowell, Silvia Rodriguez-Marin, Christopher M. Pask, Stuart L. Warriner, Thomas A. Edwards and Andrew J. Wilson

Chem. Sci., 2016, 7, 3694
DOI: 10.1039/C5SC04048E

Bioconjugation – using selective chemistry to enhance the properties of proteins and peptides as therapeutics and carriers

Smita B. Gunnoo and Annemieke Madder

Org. Biomol. Chem., 2016, 14, 8002
DOI: 10.1039/C6OB00808A

Highly reactive bis-cyclooctyne-modified diarylethene for SPAAC-mediated cross-linking

Alexander V. Strizhak, Krishna Sharma, Oleg Babii, Sergii Afonin, Anne S. Ulrich, Igor V. Komarov and David R. Spring

Org. Biomol. Chem., 2018, 16, 8559
DOI: 10.1039/C8OB02428F

Oxetane Grafts Installed Site‐Selectively on Native Disulfides to Enhance Protein Stability and Activity In Vivo

Nuria Martínez‐Sáez, Shuang Sun, Davide Oldrini, Pietro Sormanni, Omar Boutureira, Filippo Carboni, Ismael Compañón, Michael J. Deery, Michele Vendruscolo, Francisco Corzana, Roberto Adamo and Gonçalo J. L. Bernardes

Angew Chem Int Ed, 2017, 56, 14963
DOI: 10.1002/anie.201708847

Molecular engineering of designer diabetes therapeutics

Emily L. DeWolf, Bernice Webber and Matthew J. Webber

Journal of Controlled Release, 2026, 392, 114705
DOI: 10.1016/j.jconrel.2026.114705

Site-Selective Polyfluoroaryl Modification and Unsymmetric Stapling of Unprotected Peptides

Mengran Wang, Da Pan, Qi Zhang, Yongjia Lei, Chao Wang, Haoyuan Jia, Lingyun Mou, Xiaokang Miao, Xiaoyu Ren and Zhaoqing Xu

J. Am. Chem. Soc., 2024, 146, 6675
DOI: 10.1021/jacs.3c12879

Multicomponent Peptide Stapling as a Diversity‐Driven Tool for the Development of Inhibitors of Protein–Protein Interactions

Manuel G. Ricardo, Ameena M. Ali, Jacek Plewka, Ewa Surmiak, Beata Labuzek, Constantinos G. Neochoritis, Jack Atmaj, Lukasz Skalniak, Ran Zhang, Tad A. Holak, Matthew Groves, Daniel G. Rivera and Alexander Dömling

Angewandte Chemie, 2020, 132, 5273
DOI: 10.1002/ange.201916257

Recent structural advances in constrained helical peptides

Kornelia J. Skowron, Thomas E. Speltz and Terry W. Moore

Medicinal Research Reviews, 2019, 39, 749
DOI: 10.1002/med.21540

A Thiol–Ene Coupling Approach to Native Peptide Stapling and Macrocyclization

Yuanxiang Wang and Danny Hung‐Chieh Chou

Angewandte Chemie, 2015, 127, 11081
DOI: 10.1002/ange.201503975

Therapeutic Peptides, Proteins and their Nanostructures for Drug Delivery and Precision Medicine

HaRam Kim, Boghos Taslakjian, Sarah Kim, Matthew V. Tirrell and Mustafa O. Guler

ChemBioChem, 2024, 25
DOI: 10.1002/cbic.202300831

Two‐Component Stapling of Biologically Active and Conformationally Constrained Peptides: Past, Present, and Future

Jessica Iegre, Josephine S. Gaynord, Naomi S. Robertson, Hannah F. Sore, Marko Hyvönen and David R. Spring

Advanced Therapeutics, 2018, 1
DOI: 10.1002/adtp.201800052

Incorporation of Non-Canonical Amino Acids into Antimicrobial Peptides: Advances, Challenges, and Perspectives

Yuhui Du, Li Li, Yue Zheng, Jiaheng Liu, Julia Gong, Zekai Qiu, Yanni Li, Jianjun Qiao, Yi-Xin Huo and Charles M. Dozois

Appl Environ Microbiol, 2022, 88
DOI: 10.1128/aem.01617-22

1,2,3-Triazole Rings as a Disulfide Bond Mimetic in Chimeric AGRP-Melanocortin Peptides: Design, Synthesis, and Functional Characterization

Srinivasa R. Tala, Anamika Singh, Cody J. Lensing, Sathya M. Schnell, Katie T. Freeman, James R. Rocca and Carrie Haskell-Luevano

ACS Chem. Neurosci., 2018, 9, 1001
DOI: 10.1021/acschemneuro.7b00422

A Multicomponent Stapling Approach to Exocyclic Functionalized Helical Peptides: Adding Lipids, Sugars, PEGs, Labels, and Handles to the Lactam Bridge

Aldrin V. Vasco, Yanira Méndez, Andrea Porzel, Jochen Balbach, Ludger A. Wessjohann and Daniel G. Rivera

Bioconjugate Chem., 2019, 30, 253
DOI: 10.1021/acs.bioconjchem.8b00906

Synthesis and Reactivity of a Bis-Strained Alkyne Derived from 1,1′-Biphenyl-2,2′,6,6′-tetrol

Richard C. Knighton, Krishna Sharma, Naomi S. Robertson, David R. Spring and Martin Wills

ACS Omega, 2019, 4, 2160
DOI: 10.1021/acsomega.8b03634

Chiral Sulfoxide-Induced Single Turn Peptide α-Helicity

Qingzhou Zhang, Fan Jiang, Bingchuan Zhao, Huacan Lin, Yuan Tian, Mingsheng Xie, Guoyun Bai, Adam M. Gilbert, Gilles H. Goetz, Spiros Liras, Alan A. Mathiowetz, David A. Price, Kun Song, Meihua Tu, Yujie Wu, Tao Wang, Mark E. Flanagan, Yun-Dong Wu and Zigang Li

Sci Rep, 2016, 6
DOI: 10.1038/srep38573

Peptide Stapling Using Sonogashira Coupling

Devki Nandan, Susanta Kumar Behera and Ramesh Ramapanicker

ChemBioChem, 2025, 26
DOI: 10.1002/cbic.202500041

Different stapling-based peptide drug design: Mimicking α-helix as inhibitors of protein–protein interaction

Xiang Li, Yan Zou and Hong-Gang Hu

Chinese Chemical Letters, 2018, 29, 1088
DOI: 10.1016/j.cclet.2018.01.018

Peptide therapeutics: Targeting the undruggable space

Natia Tsomaia

European Journal of Medicinal Chemistry, 2015, 94, 459
DOI: 10.1016/j.ejmech.2015.01.014

Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde

Bo Li, Hong Tang, Aneta Turlik, Zhao Wan, Xiao‐Song Xue, Li Li, Xiaoxiao Yang, Jiuyuan Li, Gang He, Kendall N. Houk and Gong Chen

Angew Chem Int Ed, 2021, 60, 6646
DOI: 10.1002/anie.202016267

Advances in clinical studies of peptide drugs in stroke disease

Yan Huo, Zhe Zhang, Suzhen Dong, Yijie Du and Mingliang Ma

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2025, 1871, 167970
DOI: 10.1016/j.bbadis.2025.167970

Divinylsulfonamides as Specific Linkers for Stapling Disulfide Bonds in Peptides

Zhihong Li, Rong Huang, Hongtao Xu, Jiakang Chen, Yuexiong Zhan, Xianhao Zhou, Hongli Chen and Biao Jiang

Org. Lett., 2017, 19, 4972
DOI: 10.1021/acs.orglett.7b02464

Efficient Amino‐Sulfhydryl Stapling on Peptides and Proteins Using Bifunctional NHS‐Activated Acrylamides

Maria J. S. A. Silva, Hélio Faustino, Jaime A. S. Coelho, Maria V. Pinto, Adelaide Fernandes, Ismael Compañón, Francisco Corzana, Gilles Gasser and Pedro M. P. Gois

Angew Chem Int Ed, 2021, 60, 10850
DOI: 10.1002/anie.202016936

Enhanced Permeability and Binding Activity of Isobutylene‐Grafted Peptides

Shuang Sun, Ismael Compañón, Nuria Martínez‐Sáez, João D. Seixas, Omar Boutureira, Francisco Corzana and Gonçalo J. L. Bernardes

ChemBioChem, 2018, 19, 48
DOI: 10.1002/cbic.201700586

Guanidinium‐Stapled Helical Peptides for Targeting Protein‐Protein Interactions

Camille Perdriau, Anaïs Luton, Katharina Zimmeter, Maxime Neuville, Claire Saragaglia, Carole Peluso‐Iltis, Judit Osz, Brice Kauffmann, Gavin W. Collie, Natacha Rochel, Gilles Guichard and Morgane Pasco

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202416348

Hypervalent Iodine Amino Acid Building Blocks for Bioorthogonal Peptide Macrocyclization

Xing‐Yu Liu, Olha Mykhailenko, Adriana Faraone and Jerome Waser

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202404747

Peptide Macrocycles Developed from Precisely Regulated Multiple Cyclization of Unprotected Peptides

Jinghui Wang, Mirao Zha, Qianran Fei, Weidong Liu, Yibing Zhao and Chuanliu Wu

Chemistry A European J, 2017, 23, 15150
DOI: 10.1002/chem.201703139

Guanidinium‐Stapled Helical Peptides for Targeting Protein‐Protein Interactions

Camille Perdriau, Anaïs Luton, Katharina Zimmeter, Maxime Neuville, Claire Saragaglia, Carole Peluso‐Iltis, Judit Osz, Brice Kauffmann, Gavin W. Collie, Natacha Rochel, Gilles Guichard and Morgane Pasco

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202416348

Crosslinked Aspartic Acids as Helix‐Nucleating Templates

Hui Zhao, Qi‐Song Liu, Hao Geng, Yuan Tian, Min Cheng, Yan‐Hong Jiang, Ming‐Sheng Xie, Xiao‐Gang Niu, Fan Jiang, Ya‐Ou Zhang, Yuan‐Zhi Lao, Yun‐Dong Wu, Nai‐Han Xu and Zi‐Gang Li

Angewandte Chemie, 2016, 128, 12267
DOI: 10.1002/ange.201606833

A Method to Calculate the Relative Binding Free Energy Differences of α-Helical Stapled Peptides

Pedro A Valiente, David Becerra and Philip M Kim

J. Org. Chem., 2020, 85, 1644
DOI: 10.1021/acs.joc.9b03067

Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde

Bo Li, Hong Tang, Aneta Turlik, Zhao Wan, Xiao‐Song Xue, Li Li, Xiaoxiao Yang, Jiuyuan Li, Gang He, Kendall N. Houk and Gong Chen

Angewandte Chemie, 2021, 133, 6720
DOI: 10.1002/ange.202016267

Advances in the synthesis of cyclic peptides, pseudopeptides, and peptoids by CuAAC-mediated macrocyclization

Michael Quagliata, Paolo Rovero, Michael Chorev and Anna Maria Papini

Trends in Chemistry, 2025, 7, 276
DOI: 10.1016/j.trechm.2025.04.004

Double Strain‐Promoted Macrocyclization for the Rapid Selection of Cell‐Active Stapled Peptides

Yu Heng Lau, Yuteng Wu, Maxim Rossmann, Ban Xiong Tan, Peterson de Andrade, Yaw Sing Tan, Chandra Verma, Grahame J. McKenzie, Ashok R. Venkitaraman, Marko Hyvönen and David R. Spring

Angew Chem Int Ed, 2015, 54, 15410
DOI: 10.1002/anie.201508416

Reversibly switching the conformation of short peptide through in-tether chiral sulfonium auxiliary

Xiaodong Shi, Yixiang Jiang, Dan Yang, Hui Zhao, Yuan Tian and Zigang Li

Chinese Chemical Letters, 2018, 29, 485
DOI: 10.1016/j.cclet.2017.07.003

Phage Selection of Chemically Stabilized α-Helical Peptide Ligands

Philippe Diderich, Davide Bertoldo, Pierre Dessen, Maola M. Khan, Irene Pizzitola, Werner Held, Joerg Huelsken and Christian Heinis

ACS Chem. Biol., 2016, 11, 1422
DOI: 10.1021/acschembio.5b00963

Peptidomimetics: A Synthetic Tool for Inhibiting Protein–Protein Interactions in Cancer

Lloyd Mabonga and Abidemi Paul Kappo

Int J Pept Res Ther, 2020, 26, 225
DOI: 10.1007/s10989-019-09831-5

Ras-Targeting Stabilized Peptide Increases Radiation Sensitivity of Cancer Cells

Weirong Qin, Xiangzan Wei, Dan Yang, Qinhong Luo, Mingyu Huang, Shangping Xing, Wei Wei, Lin Liang, Jin Huang, Ziyuan Zhou and Fei Lu

Bioconjugate Chem., 2024, 35, 737
DOI: 10.1021/acs.bioconjchem.4c00155

Locking Interconversion of Aromatic Oligoamide Foldamers by Intramolecular Side‐chain Crosslinking: toward Absolute Control of Helicity in Synthetic Aromatic Foldamers

Lu Zheng, Chengyuan Yu, Yulin Zhan, Xuebin Deng, Ying Wang and Hua Jiang

Chemistry A European J, 2017, 23, 5361
DOI: 10.1002/chem.201700134

Challenge to overcome current limitations of cell-penetrating peptides

Gyu Chan Kim, Dae Hee Cheon and Yan Lee

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2021, 1869, 140604
DOI: 10.1016/j.bbapap.2021.140604

Multicomponent Reaction Toolbox for Peptide Macrocyclization and Stapling

Leslie Reguera and Daniel G. Rivera

Chem. Rev., 2019, 119, 9836
DOI: 10.1021/acs.chemrev.8b00744

Ultrashort All-Hydrocarbon Stapled α-Helix Amphiphile as a Potent and Stable Antimicrobial Compound

Changxuan Shao, Qiao Jian, Bowen Li, Yongjie Zhu, Weikang Yu, Zhongyu Li and Anshan Shan

J. Med. Chem., 2023, 66, 11414
DOI: 10.1021/acs.jmedchem.3c00856

An In‐tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide

Kuan Hu, Hao Geng, Qingzhou Zhang, Qisong Liu, Mingsheng Xie, Chengjie Sun, Wenjun Li, Huacan Lin, Fan Jiang, Tao Wang, Yun‐Dong Wu and Zigang Li

Angewandte Chemie, 2016, 128, 8145
DOI: 10.1002/ange.201602806

Solid phase diversity‐oriented lysine modification of cyclic peptides

Rongtong Zhao, Xiaodong Shi, Linlin Shi, Hui Zhao, Feng Yin and Zigang Li

Journal of Peptide Science, 2022, 28
DOI: 10.1002/psc.3373

Membrane-Active All-Hydrocarbon-Stapled α-Helical Amphiphilic Tat Peptides: Broad-Spectrum Antibacterial Activity and Low Incidence of Drug Resistance

Shu Li, Zhaopeng Wang, Shibo Song, Yuanyuan Tang, Jingjing Zhou, Xiaojing Liu, Xingjiao Zhang, Min Chang, Kairong Wang and Yali Peng

ACS Infect. Dis., 2024, 10, 1839
DOI: 10.1021/acsinfecdis.4c00173

Stitched α-Helical Peptides via Bis Ring-Closing Metathesis

Gerard J. Hilinski, Young-Woo Kim, Jooyeon Hong, Peter S. Kutchukian, Charisse M. Crenshaw, Shaunna S. Berkovitch, Andrew Chang, Sihyun Ham and Gregory L. Verdine

J. Am. Chem. Soc., 2014, 136, 12314
DOI: 10.1021/ja505141j

A Physical Organic Approach to Tuning Reagents for Selective and Stable Methionine Bioconjugation

Alec H. Christian, Shang Jia, Wendy Cao, Patricia Zhang, Arismel Tena Meza, Matthew S. Sigman, Christopher J. Chang and F. Dean Toste

J. Am. Chem. Soc., 2019, 141, 12657
DOI: 10.1021/jacs.9b04744

The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering

Sally Yunsun Kim, Alice Hai May Wong, Ensanya Ali Abou Neel, Wojciech Chrzanowski and Hak-Kim Chan

Expert Opinion on Drug Delivery, 2015, 12, 869
DOI: 10.1517/17425247.2015.993314

Peptide Stapling through Site-Directed Conjugation of Triazine Moieties to the Tyrosine Residues of a Peptide

Yue Zhang, Ruijuan Yin, Hao Jiang, Chaoming Wang, Xiao Wang, Dongping Wang, Kai Zhang, Rilei Yu, Xuechen Li and Tao Jiang

Org. Lett., 2023, 25, 2248
DOI: 10.1021/acs.orglett.3c00499

Stapled Helical Peptides Bearing Different Anchoring Residues

Xiang Li, Si Chen, Wei-Dong Zhang and Hong-Gang Hu

Chem. Rev., 2020, 120, 10079
DOI: 10.1021/acs.chemrev.0c00532

Evolution of Potential Antimitotic Stapled Peptides from Multiple Helical Peptide Stretches of the Tubulin Heterodimer Interface: Helix-Mimicking Stapled Peptide Tubulin Inhibitors

Anindyasundar Adak, Gaurav Das, Varsha Gupta, Juhee Khan, Nabanita Mukherjee, Prasenjit Mondal, Rajsekhar Roy, Surajit Barman, Prabir Kumar Gharai and Surajit Ghosh

J. Med. Chem., 2022, 65, 13866
DOI: 10.1021/acs.jmedchem.2c01116

Directed Evolution Using Stabilized Bacterial Peptide Display

Tejas Navaratna, Lydia Atangcho, Mukesh Mahajan, Vivekanandan Subramanian, Marshall Case, Andrew Min, Daniel Tresnak and Greg M. Thurber

J. Am. Chem. Soc., 2020, 142, 1882
DOI: 10.1021/jacs.9b10716

Bis‐Lactam Peptide [i, i + 4]‐Stapling

Xiao Hu, Bo Wu and Weiping Zheng

Chin. J. Chem., 2019, 37, 244
DOI: 10.1002/cjoc.201800446

Dissecting the geometric and hydrophobic constraints of stapled peptides

Jianguo Li, Yaw Sing Tan and Chandra S Verma

Proteins, 2025, 93, 287
DOI: 10.1002/prot.26662

One-pot Synthesis and Photoswitching Properties of Bis-triazole-linked Macrocyclic Glycoazobenzene

Corentin Ludwig, Gaoyu Li, Pascal Retailleau, Stéphane Maisonneuve and Juan Xie

Synthesis, 2025, 57, 2727
DOI: 10.1055/a-2637-5758

Examination of the Effect of N‐terminal Diproline and Charged Side Chains on the Stabilization of Helical Conformation in Alanine–based Short Peptides: A Molecular Dynamics Study

Bhupesh Goyal, Kinshuk Raj Srivastava and Susheel Durani

ChemistrySelect, 2016, 1, 6321
DOI: 10.1002/slct.201601381

Діарилетеновмісні “степлені” пептиди – інгібітори p53/MDM2 взаємодії

Ю.В. Баканович, О.В. Стрижак, І.В. Комаров and В.П. Хиля

Dopov. Nac. akad. nauk Ukr., 2024, 52
DOI: 10.15407/dopovidi2020.07.052

An In‐tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide

Kuan Hu, Hao Geng, Qingzhou Zhang, Qisong Liu, Mingsheng Xie, Chengjie Sun, Wenjun Li, Huacan Lin, Fan Jiang, Tao Wang, Yun‐Dong Wu and Zigang Li

Angew Chem Int Ed, 2016, 55, 8013
DOI: 10.1002/anie.201602806

Diversity‐Oriented Peptide Stapling: A Third Generation Copper‐Catalysed Azide–Alkyne Cycloaddition Stapling and Functionalisation Strategy

Phuong Thu Tran, Christian Ørnbøl Larsen, Tobias Røndbjerg, Martina De Foresta, Micha B. A. Kunze, Ales Marek, Jacob Hartvig Løper, Lotte‐Emilie Boyhus, Astrid Knuhtsen, Kresten Lindorff‐Larsen and Daniel Sejer Pedersen

Chemistry A European J, 2017, 23, 3490
DOI: 10.1002/chem.201700128

Stapled peptides: targeting protein-protein interactions in drug development

Qian Zhang, Ziyang Wang, Xiaohan Mei, Quan Chen and Chunqiu Zhang

Explor Drug Sci, 2024, 154
DOI: 10.37349/eds.2024.00041

An enhanced functional interrogation/manipulation of intracellular signaling pathways with the peptide ‘stapling’ technology

Y He, D Chen and W Zheng

Oncogene, 2015, 34, 5685
DOI: 10.1038/onc.2015.37

Macrocyclized Extended Peptides: Inhibiting the Substrate-Recognition Domain of Tankyrase

Wenshu Xu, Yu Heng Lau, Gerhard Fischer, Yaw Sing Tan, Anasuya Chattopadhyay, Marc de la Roche, Marko Hyvönen, Chandra Verma, David R. Spring and Laura S. Itzhaki

J. Am. Chem. Soc., 2017, 139, 2245
DOI: 10.1021/jacs.6b10234

Dual-Purpose Linker for Alpha Helix Stabilization and Imaging Agent Conjugation to Glucagon-Like Peptide-1 Receptor Ligands

Liang Zhang, Tejas Navaratna, Jianshan Liao and Greg M. Thurber

Bioconjugate Chem., 2015, 26, 329
DOI: 10.1021/bc500584t

Potential Self-Peptide Inhibitors of the SARS-CoV-2 Main Protease

Arkadeep Banerjee and Shachi Gosavi

J. Phys. Chem. B, 2023, 127, 855
DOI: 10.1021/acs.jpcb.2c05917

A New Methodology for Incorporating Chiral Linkers into Stapled Peptides

Juan C. Serrano, James Sipthorp, Wenshu Xu, Laura S. Itzhaki and Steven V. Ley

ChemBioChem, 2017, 18, 1066
DOI: 10.1002/cbic.201700075

Oxetane Grafts Installed Site‐Selectively on Native Disulfides to Enhance Protein Stability and Activity In Vivo

Nuria Martínez‐Sáez, Shuang Sun, Davide Oldrini, Pietro Sormanni, Omar Boutureira, Filippo Carboni, Ismael Compañón, Michael J. Deery, Michele Vendruscolo, Francisco Corzana, Roberto Adamo and Gonçalo J. L. Bernardes

Angewandte Chemie, 2017, 129, 15159
DOI: 10.1002/ange.201708847

Synthesis and Structural Stability of α-Helical Gold(I)-Metallopeptidesy

Lydia Zengerling, Benedict Kemper, Ute A. Hellmich and Pol Besenius

Synlett, 2021, 32, 344
DOI: 10.1055/a-1290-8412

Bridged Analogues for p53-Dependent Cancer Therapy Obtained by S-Alkylation

Ewa D. Micewicz, Shantanu Sharma, Alan J. Waring, Hai T. Luong, William H. McBride and Piotr Ruchala

Int J Pept Res Ther, 2016, 22, 67
DOI: 10.1007/s10989-015-9487-3

Designing stapled peptides to inhibit protein‐protein interactions: An analysis of successes in a rapidly changing field

Marie T. J. Bluntzer, James O'Connell, Terry S. Baker, Julien Michel and Alison N. Hulme

Peptide Science, 2021, 113
DOI: 10.1002/pep2.24191

Rapid Evaluation of Staple Placement in Stabilized α Helices Using Bacterial Surface Display

Marshall Case, Tejas Navaratna, Jordan Vinh and Greg Thurber

ACS Chem. Biol., 2023, 18, 905
DOI: 10.1021/acschembio.3c00048

Effect of Stapling Architecture on Physiochemical Properties and Cell Permeability of Stapled α‐Helical Peptides: A Comparative Study

Yuan Tian, Yanhong Jiang, Jingxu Li, Dongyuan Wang, Hui Zhao and Zigang Li

ChemBioChem, 2017, 18, 2087
DOI: 10.1002/cbic.201700352

Targeting the Genome‐Stability Hub Ctf4 by Stapled‐Peptide Design

Yuteng Wu, Fabrizio Villa, Joseph Maman, Yu Heng Lau, Lina Dobnikar, Aline C. Simon, Karim Labib, David R. Spring and Luca Pellegrini

Angewandte Chemie, 2017, 129, 13046
DOI: 10.1002/ange.201705611

A Peptide Stapling Strategy with Built‐In Fluorescence by Direct Late‐Stage C(sp2)−H Olefination of Tryptophan

Jiang Liu, Xin Liu, Fangfang Zhang, Jiaojiao Qu, Hongyan Sun and Qing Zhu

Chemistry A European J, 2020, 26, 16122
DOI: 10.1002/chem.202003548

Azide‐rich peptides via an on‐resin diazotransfer reaction

Jeannette E. Marine, Xiaoli Liang, Shuang Song and Jonathan G. Rudick

Biopolymers, 2015, 104, 419
DOI: 10.1002/bip.22634

Non-symmetric stapling of native peptides

Fa-Jie Chen, Wanzhen Lin and Fen-Er Chen

Nat Rev Chem, 2024, 8, 304
DOI: 10.1038/s41570-024-00591-5

Reversible and Versatile On-Tether Modification of Chiral-Center-Induced Helical Peptides

Kuan Hu, Chengjie Sun and Zigang Li

Bioconjugate Chem., 2017, 28, 2001
DOI: 10.1021/acs.bioconjchem.7b00321

Structural Studies of a Stapled Peptide with Native Ion Mobility-Mass Spectrometry and Transition Metal Ion Förster Resonance Energy Transfer in the Gas Phase

Ri Wu, Jonas B. Metternich, Prince Tiwari, Lukas R. Benzenberg, Julian A. Harrison, Qinlei Liu and Renato Zenobi

J. Am. Chem. Soc., 2022, 144, 14441
DOI: 10.1021/jacs.2c02776

Development of Cell‐Permeable, Non‐Helical Constrained Peptides to Target a Key Protein–Protein Interaction in Ovarian Cancer

Mareike M. Wiedmann, Yaw Sing Tan, Yuteng Wu, Shintaro Aibara, Wenshu Xu, Hannah F. Sore, Chandra S. Verma, Laura Itzhaki, Murray Stewart, James D. Brenton and David R. Spring

Angew Chem Int Ed, 2017, 56, 524
DOI: 10.1002/anie.201609427

Tackling Undruggable Targets with Designer Peptidomimetics and Synthetic Biologics

Colin S. Swenson, Gunasheil Mandava, Deborah M. Thomas and Raymond E. Moellering

Chem. Rev., 2024, 124, 13020
DOI: 10.1021/acs.chemrev.4c00423

Stapled peptide design: principles and roles of computation

Yaw Sing Tan, David P. Lane and Chandra S. Verma

Drug Discovery Today, 2016, 21, 1642
DOI: 10.1016/j.drudis.2016.06.012

Application of Thiol–yne/Thiol–ene Reactions for Peptide and Protein Macrocyclizations

Yuanxiang Wang, Benjamin J. Bruno, Sean Cornillie, Jason M. Nogieira, Diao Chen, Thomas E. Cheatham, Carol S. Lim and Danny Hung‐Chieh Chou

Chemistry A European J, 2017, 23, 7087
DOI: 10.1002/chem.201700572

A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies

Xiaoshu Jing and Kang Jin

Medicinal Research Reviews, 2020, 40, 753
DOI: 10.1002/med.21639

Recent Advances in Late‐Stage Construction of Stapled Peptides via C−H Activation

Jiang Liu, Peng Wang, Zhengqing Yan, Jiahui Yan, Kenry and Qing Zhu

ChemBioChem, 2021, 22, 2762
DOI: 10.1002/cbic.202100044

Macrocyclic Control in Helix Mimetics

Danielle A. Guarracino, Jacob A. Riordan, Gianna M. Barreto, Alexis L. Oldfield, Christopher M. Kouba and Desiree Agrinsoni

Chem. Rev., 2019, 119, 9915
DOI: 10.1021/acs.chemrev.8b00623

Using Peptidomimetics and Constrained Peptides as Valuable Tools for Inhibiting Protein–Protein Interactions

Naomi S. Robertson and David R. Spring

Molecules, 2018, 23, 959
DOI: 10.3390/molecules23040959

Glycinamide‐Driven Coumarin Construction (GDCC): A Mild Strategy for Fluorescent Labeling and Macrocyclization of Peptides

Xiao‐Fei Gao, Wei Xiao, Tian‐Ming Tao, Feng‐Cai Ma, Xiao‐Yan Liu, Xue Jiang, Zhong‐Hong Liu, Xing‐Lei Zhang, Yu Chai, Emeric Miclet, Valérie Alezra, Yuan‐Biao Tu, Qi‐Dong Tu, Yang Wan, Hai‐Sheng Wang and Qiang Xiao

Angew Chem Int Ed, 2026, 65
DOI: 10.1002/anie.202525302

Acetone‐Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling

Naila Assem, David J. Ferreira, Dennis W. Wolan and Philip E. Dawson

Angew Chem Int Ed, 2015, 54, 8665
DOI: 10.1002/anie.201502607

Hitting Undruggable Targets: Viewing Stabilized Peptide Development through the Lens of Quantitative Systems Pharmacology

Lydia Atangcho, Tejas Navaratna and Greg M. Thurber

Trends in Biochemical Sciences, 2019, 44, 241
DOI: 10.1016/j.tibs.2018.11.008

Nitrogen Arylation for Macrocyclization of Unprotected Peptides

Guillaume Lautrette, Fayçal Touti, Hong Geun Lee, Peng Dai and Bradley L. Pentelute

J. Am. Chem. Soc., 2016, 138, 8340
DOI: 10.1021/jacs.6b03757

The Synthesis of Structurally Diverse Macrocycles By Successive Ring Expansion

Christiana Kitsiou, Jordan J. Hindes, Phillip I'Anson, Paula Jackson, Thomas C. Wilson, Eleanor K. Daly, Hannah R. Felstead, Peter Hearnshaw and William P. Unsworth

Angew Chem Int Ed, 2015, 54, 15794
DOI: 10.1002/anie.201509153

Development of Cell‐Permeable, Non‐Helical Constrained Peptides to Target a Key Protein–Protein Interaction in Ovarian Cancer

Mareike M. Wiedmann, Yaw Sing Tan, Yuteng Wu, Shintaro Aibara, Wenshu Xu, Hannah F. Sore, Chandra S. Verma, Laura Itzhaki, Murray Stewart, James D. Brenton and David R. Spring

Angewandte Chemie, 2017, 129, 539
DOI: 10.1002/ange.201609427

Facile Chemoselective Modification of Thio-Ethers Generates Chiral Center-Induced Helical Peptides

Zhanfeng Hou, Chengjie Sun, Hao Geng, Kuan Hu, Mingsheng Xie, Yue Ma, Fan Jiang, Feng Yin and Zigang Li

Bioconjugate Chem., 2018, 29, 2904
DOI: 10.1021/acs.bioconjchem.8b00624

Tuning the Binding Affinity and Selectivity of Perfluoroaryl‐Stapled Peptides by Cysteine‐Editing

Sanne J. M. Verhoork, Claire E. Jennings, Neshat Rozatian, Judith Reeks, Jieman Meng, Emily K. Corlett, Fazila Bunglawala, Martin E. M. Noble, Andrew G. Leach and Christopher R. Coxon

Chemistry A European J, 2019, 25, 177
DOI: 10.1002/chem.201804163

Exploiting the Potential of Iridium(III) bis-Nitrone Complexes as Phosphorogenic Bifunctional Reagents for Phototheranostics

Eunice Chiu-Lam Mak, Ziyong Chen, Lawrence Cho-Cheung Lee, Peter Kam-Keung Leung, Alex Man-Hei Yip, Justin Shum, Shek-Man Yiu, Vivian Wing-Wah Yam and Kenneth Kam-Wing Lo

J. Am. Chem. Soc., 2024, 146, 25589
DOI: 10.1021/jacs.4c07251

The Synthesis of Structurally Diverse Macrocycles By Successive Ring Expansion

Christiana Kitsiou, Jordan J. Hindes, Phillip I'Anson, Paula Jackson, Thomas C. Wilson, Eleanor K. Daly, Hannah R. Felstead, Peter Hearnshaw and William P. Unsworth

Angewandte Chemie, 2015, 127, 16020
DOI: 10.1002/ange.201509153

The 1,3‐diyne linker as a rigid “i,i+7” staple for α‐helix stabilization: Stereochemistry at work

Steven Verlinden, Niels Geudens, Kevin Van holsbeeck, Morgane Mannes, José C. Martins, Guido Verniest and Steven Ballet

Journal of Peptide Science, 2019, 25
DOI: 10.1002/psc.3194

Development of cell‐penetrating peptide‐based drug leads to inhibit MDMX:p53 and MDM2:p53 interactions

Grégoire Philippe, Yen‐Hua Huang, Olivier Cheneval, Nicole Lawrence, Zhen Zhang, David P Fairlie, David J. Craik, Aline Dantas de Araujo and Sónia Troeira Henriques

Biopolymers, 2016, 106, 853
DOI: 10.1002/bip.22893

Multifunctional synthetic nano-chaperone for peptide folding and intracellular delivery

Il-Soo Park, Seongchan Kim, Yeajee Yim, Ginam Park, Jinahn Choi, Cheolhee Won and Dal-Hee Min

Nat Commun, 2022, 13
DOI: 10.1038/s41467-022-32268-2

HBx-Derived Constrained Peptides Inhibit the Secretion of Hepatitis B Virus Antigens

Xiaodan Cai, Weihao Zheng, Xiaodong Shi, Longjian Chen, Zhihong Liu and Zigang Li

Mol. Pharmaceutics, 2018, 15, 5646
DOI: 10.1021/acs.molpharmaceut.8b00807

Strukturbasierte Entwicklung von Protein‐Protein‐Interaktionsinhibitoren: Stabilisierung und Nachahmung von Peptidliganden

Marta Pelay‐Gimeno, Adrian Glas, Oliver Koch and Tom N. Grossmann

Angewandte Chemie, 2015, 127, 9022
DOI: 10.1002/ange.201412070

Development of a Multifunctional Benzophenone Linker for Peptide Stapling and Photoaffinity Labelling

Yuteng Wu, Lasse B. Olsen, Yu Heng Lau, Claus Hatt Jensen, Maxim Rossmann, Ysobel R. Baker, Hannah F. Sore, Súil Collins and David R. Spring

ChemBioChem, 2016, 17, 689
DOI: 10.1002/cbic.201500648

Dual In-Tether Chiral Centers Modulate Peptide Helicity

Kuan Hu, Chengjie Sun, Mengying Yu, Wenjun Li, Huacan Lin, Jialin Guo, Yixiang Jiang, Chengxiang Lei and Zigang Li

Bioconjugate Chem., 2017, 28, 1537
DOI: 10.1021/acs.bioconjchem.7b00171

Acetone‐Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling

Naila Assem, David J. Ferreira, Dennis W. Wolan and Philip E. Dawson

Angewandte Chemie, 2015, 127, 8789
DOI: 10.1002/ange.201502607

Overcoming Chemical, Biological, and Computational Challenges in the Development of Inhibitors Targeting Protein-Protein Interactions

Luca Laraia, Grahame McKenzie, David R. Spring, Ashok R. Venkitaraman and David J. Huggins

Chemistry & Biology, 2015, 22, 689
DOI: 10.1016/j.chembiol.2015.04.019

A two-component 'double-click' approach to peptide stapling

Yu Heng Lau, Yuteng Wu, Peterson de Andrade, Warren R J D Galloway and David R Spring

Nat Protoc, 2015, 10, 585
DOI: 10.1038/nprot.2015.033

Hypervalent Iodine Amino Acid Building Blocks for Bioorthogonal Peptide Macrocyclization

Xing‐Yu Liu, Olha Mykhailenko, Adriana Faraone and Jerome Waser

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202404747

A one-step, resin-compatible Cys-Trp cross-linking system opens a new avenue for stapled peptide therapeutics

Masaya Denda, Yutaka Kohmura, Daishiro Kobayashi, Tetsuro Yoshimaru, Shoichiro Fukuda, Hidenori Ando, Tatsuhiro Ishida, Toyomasa Katagiri and Akira Otaka

Bioorganic & Medicinal Chemistry, 2026, 137, 118622
DOI: 10.1016/j.bmc.2026.118622

A study of 2-component i, i + 3 peptide stapling using thioethers

Lauren E. St. Louis, Tayliz M. Rodriguez and Marcey L. Waters

Bioorganic & Medicinal Chemistry, 2018, 26, 1203
DOI: 10.1016/j.bmc.2017.10.037

Toolbox of Diverse Linkers for Navigating the Cellular Efficacy Landscape of Stapled Peptides

Yuteng Wu, Amandeep Kaur, Elaine Fowler, Mareike M. Wiedmann, Reginald Young, Warren R. J. D. Galloway, Lasse Olsen, Hannah F. Sore, Anasuya Chattopadhyay, Terence T.-L. Kwan, Wenshu Xu, Stephen J. Walsh, Peterson de Andrade, Matej Janecek, Senthil Arumugam, Laura S. Itzhaki, Yu Heng Lau and David R. Spring

ACS Chem. Biol., 2019, 14, 526
DOI: 10.1021/acschembio.9b00063

An Alkyne Rod to Constrain a Peptide Backbone in an Extended Conformation

Adam Přibylka and Viktor Krchňák

Eur J Org Chem, 2018, 2018, 4709
DOI: 10.1002/ejoc.201800979

1,2,3-Triazoles as Biomimetics in Peptide Science

Naima Agouram, El Mestafa El Hadrami and Abdeslem Bentama

Molecules, 2021, 26, 2937
DOI: 10.3390/molecules26102937

Gold(III) Aryl Complexes as Reagents for Constructing Hybrid Peptide-Based Assemblies via Cysteine S-Arylation

Julia M. Stauber, Arnold L. Rheingold and Alexander M. Spokoyny

Inorg. Chem., 2021, 60, 5054
DOI: 10.1021/acs.inorgchem.1c00087

Disulfide-Directed Multicyclic Peptides with N-Terminally Extendable α-Helices for Recognition and Activation of G Protein-Coupled Receptors

Shihui Fan, Jie Li, Jie Zhuang, Qingtong Zhou, Yiting Mai, Bingni Lin, Ming-Wei Wang and Chuanliu Wu

J. Am. Chem. Soc., 2025, 147, 4821
DOI: 10.1021/jacs.4c12808

Oxidative diversification of amino acids and peptides by small-molecule iron catalysis

Thomas J. Osberger, Donald C. Rogness, Jeffrey T. Kohrt, Antonia F. Stepan and M. Christina White

Nature, 2016, 537, 214
DOI: 10.1038/nature18941

Crosslinked Aspartic Acids as Helix‐Nucleating Templates

Hui Zhao, Qi‐Song Liu, Hao Geng, Yuan Tian, Min Cheng, Yan‐Hong Jiang, Ming‐Sheng Xie, Xiao‐Gang Niu, Fan Jiang, Ya‐Ou Zhang, Yuan‐Zhi Lao, Yun‐Dong Wu, Nai‐Han Xu and Zi‐Gang Li

Angew Chem Int Ed, 2016, 55, 12088
DOI: 10.1002/anie.201606833

Modification of Vancomycin Structure to Combat against Emerging Vancomycin Resistance

Cenk Serhan Ozverel, Cemile Bagkur and Emine Erdag

ChemistrySelect, 2024, 9
DOI: 10.1002/slct.202403671

Targeting the Genome‐Stability Hub Ctf4 by Stapled‐Peptide Design

Yuteng Wu, Fabrizio Villa, Joseph Maman, Yu Heng Lau, Lina Dobnikar, Aline C. Simon, Karim Labib, David R. Spring and Luca Pellegrini

Angew Chem Int Ed, 2017, 56, 12866
DOI: 10.1002/anie.201705611

Translation of Deoxyribonucleic Acid into Synthetic Alpha Helical Peptides for Darwinian Evolution

Millicent Dockerill, Pramod M. Sabale, Francesco Russo, Sofia Barluenga and Nicolas Winssinger

JACS Au, 2024, 4, 4013
DOI: 10.1021/jacsau.4c00738

Multicomponent Peptide Stapling as a Diversity‐Driven Tool for the Development of Inhibitors of Protein–Protein Interactions

Manuel G. Ricardo, Ameena M. Ali, Jacek Plewka, Ewa Surmiak, Beata Labuzek, Constantinos G. Neochoritis, Jack Atmaj, Lukasz Skalniak, Ran Zhang, Tad A. Holak, Matthew Groves, Daniel G. Rivera and Alexander Dömling

Angew Chem Int Ed, 2020, 59, 5235
DOI: 10.1002/anie.201916257

Functionalized Double Strain-Promoted Stapled Peptides for Inhibiting the p53-MDM2 Interaction

Krishna Sharma, Alexander V. Strizhak, Elaine Fowler, Wenshu Xu, Ben Chappell, Hannah F. Sore, Warren R. J. D. Galloway, Matthew N. Grayson, Yu Heng Lau, Laura S. Itzhaki and David R. Spring

ACS Omega, 2020, 5, 1157
DOI: 10.1021/acsomega.9b03459

Double Strain‐Promoted Macrocyclization for the Rapid Selection of Cell‐Active Stapled Peptides

Yu Heng Lau, Yuteng Wu, Maxim Rossmann, Ban Xiong Tan, Peterson de Andrade, Yaw Sing Tan, Chandra Verma, Grahame J. McKenzie, Ashok R. Venkitaraman, Marko Hyvönen and David R. Spring

Angewandte Chemie, 2015, 127, 15630
DOI: 10.1002/ange.201508416

Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

Marta Pelay‐Gimeno, Adrian Glas, Oliver Koch and Tom N. Grossmann

Angew Chem Int Ed, 2015, 54, 8896
DOI: 10.1002/anie.201412070

A Thiol–Ene Coupling Approach to Native Peptide Stapling and Macrocyclization

Yuanxiang Wang and Danny Hung‐Chieh Chou

Angew Chem Int Ed, 2015, 54, 10931
DOI: 10.1002/anie.201503975

Stapled Peptides—A Useful Improvement for Peptide-Based Drugs

Mattia Moiola, Misal G. Memeo and Paolo Quadrelli

Molecules, 2019, 24, 3654
DOI: 10.3390/molecules24203654

Water-Soluble Palladium Reagents for Cysteine S-Arylation under Ambient Aqueous Conditions

Anthony J. Rojas, Bradley L. Pentelute and Stephen L. Buchwald

Org. Lett., 2017, 19, 4263
DOI: 10.1021/acs.orglett.7b01911

Suprastapled Peptides: Hybridization-Enhanced Peptide Ligation and Enforced α-Helical Conformation for Affinity Selection of Combinatorial Libraries

Pramod M. Sabale, Mateusz Imiołek, Pierre Raia, Sofia Barluenga and Nicolas Winssinger

J. Am. Chem. Soc., 2021, 143, 18932
DOI: 10.1021/jacs.1c07013

Peptide-to-Small Molecule: A Pharmacophore-Guided Small Molecule Lead Generation Strategy from High-Affinity Macrocyclic Peptides

Shuhei Yoshida, Shota Uehara, Noriyasu Kondo, Yu Takahashi, Shiho Yamamoto, Atsushi Kameda, Soichiro Kawagoe, Naoko Inoue, Masami Yamada, Norito Yoshimura and Yuki Tachibana

J. Med. Chem., 2022, 65, 10655
DOI: 10.1021/acs.jmedchem.2c00919

Linker Engineering in Stapled Peptides for Enhanced Membrane Permeability: Screening and Optimization Strategies

Min Zhao, Baojian Li, Ying Gao, Rui Zhang, Subinur Ahmattohti, Jie Li and Xinbo Shi

IJMS, 2026, 27, 3077
DOI: 10.3390/ijms27073077

Bent into shape: Folded peptides to mimic protein structure and modulate protein function

Haley I. Merritt, Nicholas Sawyer and Paramjit S. Arora

Peptide Science, 2020, 112
DOI: 10.1002/pep2.24145

Unique arginine array improves cytosolic localization of hydrocarbon-stapled peptides

Kim Quach, Jonathan LaRochelle, Xiao-Han Li, Elizabeth Rhoades and Alanna Schepartz

Bioorganic & Medicinal Chemistry, 2018, 26, 1197
DOI: 10.1016/j.bmc.2017.11.008

Peptide-Based Targeted Covalent Inhibitors

Fangyu Cao, Ruo-Chen Guo, Zeyu Zhang and Zhilin Yu

ACS Appl. Mater. Interfaces, 2025, 17, 60104
DOI: 10.1021/acsami.5c18100

Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction

Md Shafiqul Islam, Samuel L. Junod, Si Zhang, Zakey Yusuf Buuh, Yifu Guan, Mi Zhao, Kishan H. Kaneria, Parmila Kafley, Carson Cohen, Robert Maloney, Zhigang Lyu, Vincent A. Voelz, Weidong Yang and Rongsheng E. Wang

Nat Commun, 2022, 13
DOI: 10.1038/s41467-022-27995-5

Linear Aliphatic Dialkynes as Alternative Linkers for Double‐Click Stapling of p53‐Derived Peptides

Yu Heng Lau, Peterson de Andrade, Grahame J. McKenzie, Ashok R. Venkitaraman and David R. Spring

ChemBioChem, 2014, 15, 2680
DOI: 10.1002/cbic.201402374

Constraining and Modifying Peptides Using Pd‐Mediated Cysteine Allylation

Julia Kriegesmann, Thomas Schlatzer, Kateryna Che, Claudia Altdorf, Susanne Huhmann, Hanspeter Kählig, Dennis Kurzbach, Rolf Breinbauer and Christian F. W. Becker

ChemBioChem, 2023, 24
DOI: 10.1002/cbic.202300098

Efficient Amino‐Sulfhydryl Stapling on Peptides and Proteins Using Bifunctional NHS‐Activated Acrylamides

Maria J. S. A. Silva, Hélio Faustino, Jaime A. S. Coelho, Maria V. Pinto, Adelaide Fernandes, Ismael Compañón, Francisco Corzana, Gilles Gasser and Pedro M. P. Gois

Angewandte Chemie, 2021, 133, 10945
DOI: 10.1002/ange.202016936

Glycinamide‐Driven Coumarin Construction (GDCC): A Mild Strategy for Fluorescent Labeling and Macrocyclization of Peptides

Xiao‐Fei Gao, Wei Xiao, Tian‐Ming Tao, Feng‐Cai Ma, Xiao‐Yan Liu, Xue Jiang, Zhong‐Hong Liu, Xing‐Lei Zhang, Yu Chai, Emeric Miclet, Valérie Alezra, Yuan‐Biao Tu, Qi‐Dong Tu, Yang Wan, Hai‐Sheng Wang and Qiang Xiao

Angewandte Chemie, 2026, 138
DOI: 10.1002/ange.202525302

Palladium Oxidative Addition Complexes for Peptide and Protein Cross-linking

Koji Kubota, Peng Dai, Bradley L. Pentelute and Stephen L. Buchwald

J. Am. Chem. Soc., 2018, 140, 3128
DOI: 10.1021/jacs.8b00172

Macrocyclization of Unprotected Peptide Isocyanates

Alexander A. Vinogradov, Zi-Ning Choo, Kyle A. Totaro and Bradley L. Pentelute

Org. Lett., 2016, 18, 1226
DOI: 10.1021/acs.orglett.5b03626

A Helix-Stabilizing Linker Improves Subcutaneous Bioavailability of a Helical Peptide Independent of Linker Lipophilicity

Liang Zhang, Tejas Navaratna and Greg M. Thurber

Bioconjugate Chem., 2016, 27, 1663
DOI: 10.1021/acs.bioconjchem.6b00209

Exploring the Effect of Hydrocarbon Cross‐Linkers on the Structure and Binding of Stapled p53 Peptides

Asha Rani Choudhury, Vikram Gaikwad, Atanu Maity and Rajarshi Chakrabarti

Proteins, 2025, 93, 1090
DOI: 10.1002/prot.26793

Recent Chemical Biology Insights Towards Reversible Stapled Peptides

Ying Chen, Chuan Dai, Jinyan Han, Yun Xing, Feng Yin and Zigang Li

ChemBioChem, 2025, 26
DOI: 10.1002/cbic.202500052