Sequential conjugation methods based on triazole formation and related reactions using azides

Suguru Yoshida

Org. Biomol. Chem., 2020, 18, 1550
DOI: 10.1039/C9OB02698C

Chemical technology principles for selective bioconjugation of proteins and antibodies

Preeti Chauhan, Ragendu V., Mohan Kumar, Rajib Molla, Surya Dev Mishra, Sneha Basa and Vishal Rai

Chem. Soc. Rev., 2024, 53, 380
DOI: 10.1039/D3CS00715D

The mechanism behind enhanced reactivity of unsaturated phosphorus(v) electrophiles towards thiols

Yerin Park, Alice L. Baumann, Hyejin Moon, Stephen Byrne, Marc-André Kasper, Songhwan Hwang, Han Sun, Mu-Hyun Baik and Christian P. R. Hackenberger

Chem. Sci., 2021, 12, 8141
DOI: 10.1039/D1SC01730F

Biocompatible strategies for peptide macrocyclisation

Junming He, Pritha Ghosh and Christoph Nitsche

Chem. Sci., 2024, 15, 2300
DOI: 10.1039/D3SC05738K

Modular solid-phase synthesis of electrophilic cysteine-selective ethynyl-phosphonamidate peptides

Sarah Hansen, Jan Vincent V. Arafiles, Philipp Ochtrop and Christian P. R. Hackenberger

Chem. Commun., 2022, 58, 8388
DOI: 10.1039/D2CC02379B

Site-selective modification strategies in antibody–drug conjugates

Stephen J. Walsh, Jonathan D. Bargh, Friederike M. Dannheim, Abigail R. Hanby, Hikaru Seki, Andrew J. Counsell, Xiaoxu Ou, Elaine Fowler, Nicola Ashman, Yuri Takada, Albert Isidro-Llobet, Jeremy S. Parker, Jason S. Carroll and David R. Spring

Chem. Soc. Rev., 2021, 50, 1305
DOI: 10.1039/D0CS00310G

A platform for SpyCatcher conjugation to native antibodies

Sona Krajcovicova, Thomas Wharton, Claudia L. Driscoll, Thomas A. King, Mark R. Howarth and David R. Spring

Chem. Sci., 2025, 16, 10602
DOI: 10.1039/D5SC02286J

α-Vinyl azide–cysteine click coupling reaction enabled bioorthogonal peptide/protein modification

Mei-Hua Shen, Yu-Jiao Wang, Yong Wang, Ying Zhou, Jie Gu, Xiao-Qian Liu, Jia Guo, Mingxing Ouyang, Linhong Deng and Hua-Dong Xu

Org. Chem. Front., 2022, 9, 4654
DOI: 10.1039/D2QO00736C

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

Compact hydrophilic electrophiles enable highly efficacious high DAR ADCs with excellent in vivo PK profile

Philipp Ochtrop, Jahaziel Jahzerah, Paul Machui, Isabelle Mai, Dominik Schumacher, Jonas Helma, Marc-André Kasper and Christian P. R. Hackenberger

Chem. Sci., 2023, 14, 2259
DOI: 10.1039/D2SC05678J

S-Alkylation of cysteine-containing peptides using thianthenium salts as an alkyl source in flow

Hao Lv, Jie Liu, Long-Zhou Qin, Hao Sun, Jian Wang, Shan-Shan Zhu, Xiu Duan, Xin Yuan, Jiang-Kai Qiu and Kai Guo

Green Chem., 2024, 26, 7414
DOI: 10.1039/D4GC01638F

One‐Step Maleimide‐Based Dual Functionalization of Protein N‐Termini

Kengo Hanaya, Kazuaki Taguchi, Yuki Wada and Masaki Kawano

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202417134

Recent Advances in β-catenin/BCL9 protein–protein Interaction Inhibitors

Hao Zhang, Ya Bao, Chenglong Liu, Jianqi Li, Di Zhu and Qingwei Zhang

Future Med. Chem., 2021, 13, 927
DOI: 10.4155/fmc-2020-0357

Recent Advances in Chemical Protein Modification via Cysteine

Changliu Wang, Yongli Zhao and Junfeng Zhao

Chinese Journal of Organic Chemistry, 2022, 42, 2774
DOI: 10.6023/cjoc202203008

Unsaturated Phosphine Oxides for Modular Antibody Rebridging and Single Reagent Peptide‐Cyclization‐Bioconjugation

Christian E. Stieger, Alastair J. McMillan, Mark A. R. de Geus, Jan Vincent V. Arafiles, Luise Franz and Christian P. R. Hackenberger

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202508656

Multifluorinated Aryl Azides for the Development of Improved H2S Probes, and Fast Strain‐promoted Azide‐Alkyne Cycloaddition and Staudinger Reactions

Xueying Kang, Xuekang Cai, Long Yi and Zhen Xi

Chemistry An Asian Journal, 2020, 15, 1420
DOI: 10.1002/asia.202000005

Modular Vinyl Phosphonamidates for Cysteine-Directed Protein Targeting

Christian E. Stieger, Charlotte Völkel, Mathias B. Bertelsen, Michael Lisurek, Jan Vincent V. Arafiles, Jonathan Franke, Leander Crocker, Karl Schuppe, Yunjae Lim, Christiane Groneberg, Mathias Christmann, Han Sun and Christian P. R. Hackenberger

J. Am. Chem. Soc., 2026, 148, 7772
DOI: 10.1021/jacs.5c22349

Developing bioorthogonal probes to span a spectrum of reactivities

Sean S. Nguyen and Jennifer A. Prescher

Nat Rev Chem, 2020, 4, 476
DOI: 10.1038/s41570-020-0205-0

Fast Cysteine Bioconjugation Chemistry

Fa‐Jie Chen and Jianmin Gao

Chemistry A European J, 2022, 28
DOI: 10.1002/chem.202201843

Allenamides as a Powerful Tool to Incorporate Diversity: Thia‐Michael Lipidation of Semisynthetic Peptides and Access to β‐Keto Amides

Tae‐Ung Na, Veronika Sander, Alan J. Davidson, Rolland Lin, Yann O. Hermant, Madeleine T. Hardie Boys, Daniel Pletzer, Georgia Campbell, Scott A. Ferguson, Gregory M. Cook, Jane R. Allison, Margaret A. Brimble, Brian H. Northrop and Alan J. Cameron

Angewandte Chemie, 2024, 136
DOI: 10.1002/ange.202407764

Bioorthogonal Phosphines: Then and Now

Robert S. Dorn and Jennifer A. Prescher

Israel Journal of Chemistry, 2023, 63
DOI: 10.1002/ijch.202200070

N‐Hydroxysuccinimide‐Modified Ethynylphosphonamidates Enable the Synthesis of Configurationally Defined Protein Conjugates

Marc‐André Kasper, Marcus Gerlach, Anselm F. L. Schneider, Christiane Groneberg, Philipp Ochtrop, Stefanie Boldt, Dominik Schumacher, Jonas Helma, Heinrich Leonhardt, Mathias Christmann and Christian P. R. Hackenberger

ChemBioChem, 2020, 21, 113
DOI: 10.1002/cbic.201900587

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

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly

Hao Sun, Wei Cao, Nanzhi Zang, Tristan D. Clemons, Georg M. Scheutz, Ziying Hu, Matthew P. Thompson, Yifei Liang, Maria Vratsanos, Xuhao Zhou, Wonmin Choi, Brent S. Sumerlin, Samuel I. Stupp and Nathan C. Gianneschi

Angew Chem Int Ed, 2020, 59, 19136
DOI: 10.1002/anie.202006385

The expanding repertoire of covalent warheads for drug discovery

Namrashee V. Mehta and Mariam S. Degani

Drug Discovery Today, 2023, 28, 103799
DOI: 10.1016/j.drudis.2023.103799

Efficient Synthesis of Phosphonamidates through One‐Pot Sequential Reactions of Phosphonites with Iodine and Amines

Xunwei Chen, Wenjun Luo, Yanlin Wang, Zikang Li, Xiaorui Ma and Ai‐Yun Peng

Chemistry A European J, 2020, 26, 14474
DOI: 10.1002/chem.202002934

Expanding the payload scope in antibody-drug conjugates by delivery of hydroxy-containing drugs through self-immolative phosphoramidates

Philipp Ochtrop, Anil P. Jagtap, Jan G. Felber, Simon Vogt, Sarah Herterich, Isabelle Mai, Philipp Cyprys, Saskia Schmitt, Sarah Payer, Annabel Kitowski, Swetlana Wunder, Paul Machui, Julia Brandmeier, Natascia Leonardi, Elizaveta Poliak, Christian P. R. Hackenberger, Olivier Marcq, Dominik Schumacher, Jonas Helma, Annette M. Vogl and Marc-André Kasper

Nat Commun, 2026, 17
DOI: 10.1038/s41467-026-68605-y

One‐Step Maleimide‐Based Dual Functionalization of Protein N‐Termini

Kengo Hanaya, Kazuaki Taguchi, Yuki Wada and Masaki Kawano

Angew Chem Int Ed, 2025, 64
DOI: 10.1002/anie.202417134

Unsaturated Phosphorus Electrophiles to Probe Protein Tyrosine Phosphatases

Eleftheria Poulou, Max Ruwolt, Christian E. Stieger, Kristin Kemnitz‐Hassanin and Christian P. R. Hackenberger

Angew Chem Int Ed, 2026, 65
DOI: 10.1002/anie.202521902

Sterically‐Controlled Self‐Immolation in Phosphoramidate Linkers Triggered by Light

Eliška Procházková, Juraj Filo, Marek Cigáň and Ondřej Baszczyňski

Eur J Org Chem, 2020, 2020, 897
DOI: 10.1002/ejoc.201901882

Protein Modification of Lysine with 2-(2-Styrylcyclopropyl)ethanal

Caroline Apel, Marc-André Kasper, Christian E. Stieger, Christian P. R. Hackenberger and Mathias Christmann

Org. Lett., 2019, 21, 10043
DOI: 10.1021/acs.orglett.9b03982

Recent Advances in Bioorthogonal Ligation and Bioconjugation

Florian M. Zielke and Floris P. J. T. Rutjes

Top Curr Chem (Z), 2023, 381
DOI: 10.1007/s41061-023-00445-6

Bioorthogonal Reactions of Triarylphosphines and Related Analogues

Tyler K. Heiss, Robert S. Dorn and Jennifer A. Prescher

Chem. Rev., 2021, 121, 6802
DOI: 10.1021/acs.chemrev.1c00014

Diethinylphosphinate für die Cystein‐selektive Proteinmarkierung und Disulfid‐Verbrückung

Christian E. Stieger, Luise Franz, Frieder Körlin and Christian P. R. Hackenberger

Angewandte Chemie, 2021, 133, 15487
DOI: 10.1002/ange.202100683

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization‐Induced Self‐Assembly

Hao Sun, Wei Cao, Nanzhi Zang, Tristan D. Clemons, Georg M. Scheutz, Ziying Hu, Matthew P. Thompson, Yifei Liang, Maria Vratsanos, Xuhao Zhou, Wonmin Choi, Brent S. Sumerlin, Samuel I. Stupp and Nathan C. Gianneschi

Angewandte Chemie, 2020, 132, 19298
DOI: 10.1002/ange.202006385

(3+2)‐Cyclization Reactions of Unsaturated Phosphonites with Aldehydes and Thioketones

Don S. Munasinghe, Marc‐André Kasper, Radomir Jasiński, Karolina Kula, Marcin Palusiak, Małgorzata Celeda, Grzegorz Mlostoń and Christian P. R. Hackenberger

Chemistry A European J, 2023, 29
DOI: 10.1002/chem.202300806

Recent advances of thiol-selective bioconjugation reactions

Philipp Ochtrop and Christian Peter Richard Hackenberger

Current Opinion in Chemical Biology, 2020, 58, 28
DOI: 10.1016/j.cbpa.2020.04.017

Staudinger Ligation and Reactions – From Bioorthogonal Labeling to Next‐Generation Biopharmaceuticals

Eleftheria Poulou and Christian P. R. Hackenberger

Israel Journal of Chemistry, 2023, 63
DOI: 10.1002/ijch.202200057

DFT‐basierte Entdeckung von Ethynyl‐Triazolyl‐Phosphinaten als modulare Elektrophile für die chemoselektive Cystein‐Biokonjugation und Profilierung

Christian E. Stieger, Yerin Park, Mark A. R. de Geus, Dongju Kim, Christiane Huhn, J. Sophia Slenczka, Philipp Ochtrop, Judith M. Müchler, Roderich D. Süssmuth, Johannes Broichhagen, Mu‐Hyun Baik and Christian P. R. Hackenberger

Angewandte Chemie, 2022, 134
DOI: 10.1002/ange.202205348

Discovery of Novel 1-Phenylpiperidine Urea-Containing Derivatives Inhibiting β-Catenin/BCL9 Interaction and Exerting Antitumor Efficacy through the Activation of Antigen Presentation of cDC1 Cells

Wenhua Zhu, Cuiting Liu, Kang Xi, Anqi Li, Li-an Shen, Yana Li, Miaomiao Jia, Yangbo He, Gang Chen, Chenglong Liu, Yangqiang Chen, Kai Chen, Fan Sun, Daizhou Zhang, Chonggang Duan, Heng Wang, Dongdong Wang, Yujun Zhao, Xiangjing Meng and Di Zhu

J. Med. Chem., 2024, 67, 12485
DOI: 10.1021/acs.jmedchem.3c02079

Cell-penetrating peptides in protein mimicry and cancer therapeutics

Matjaž Zorko, Sarah Jones and Ülo Langel

Advanced Drug Delivery Reviews, 2022, 180, 114044
DOI: 10.1016/j.addr.2021.114044

Synthesis of Phosphorodiamidate Morpholino Oligonucleotides (PMOs) Using Staudinger Reduction as a Deblocking Condition and Its Usefulness for Orthogonal Conjugation in Bi- and Trifunctionalized PMOs

Subhamoy Pratihar, Md Qasim and Surajit Sinha

Synlett, 2024, 35, 2435
DOI: 10.1055/a-2384-7323

A novel β-catenin/BCL9 complex inhibitor blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer

Helen Tanton, Tomasz Sewastianik, Hyuk-Soo Seo, David Remillard, Roodolph St. Pierre, Pratyusha Bala, Daulet Aitymbayev, Peter Dennis, Keith Adler, Ezekiel Geffken, Zoe Yeoh, Nicholas Vangos, Filip Garbicz, David Scott, Nilay Sethi, James Bradner, Sirano Dhe-Paganon and Ruben D. Carrasco

Sci. Adv., 2022, 8
DOI: 10.1126/sciadv.abm3108

Medicinal Chemistry Strategies for the Development of Inhibitors Disrupting β-Catenin’s Interactions with Its Nuclear Partners

Hao Zhang, Chenglong Liu, Di Zhu, Qingwei Zhang and Jianqi Li

J. Med. Chem., 2023, 66, 1
DOI: 10.1021/acs.jmedchem.2c01016

The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

Linghui Qian, Xuefen Lin, Xue Gao, Rizwan Ullah Khan, Jia-Yu Liao, Shubo Du, Jingyan Ge, Su Zeng and Shao Q. Yao

Chem. Rev., 2023, 123, 7782
DOI: 10.1021/acs.chemrev.2c00915

Site-specific protein labeling: Recent progress

Yiming Ma, Yuanbo Wang, Fang Wang, Sheng Lu and Xiaoqiang Chen

Chinese Chemical Letters, 2025, 36, 110546
DOI: 10.1016/j.cclet.2024.110546

Chemically Induced Vinylphosphonothiolate Electrophiles for Thiol–Thiol Bioconjugations

Alice L. Baumann, Sergej Schwagerus, Kevin Broi, Kristin Kemnitz-Hassanin, Christian E. Stieger, Nils Trieloff, Peter Schmieder and Christian P. R. Hackenberger

J. Am. Chem. Soc., 2020, 142, 9544
DOI: 10.1021/jacs.0c03426

DFT‐Guided Discovery of Ethynyl‐Triazolyl‐Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling

Christian E. Stieger, Yerin Park, Mark A. R. de Geus, Dongju Kim, Christiane Huhn, J. Sophia Slenczka, Philipp Ochtrop, Judith M. Müchler, Roderich D. Süssmuth, Johannes Broichhagen, Mu‐Hyun Baik and Christian P. R. Hackenberger

Angew Chem Int Ed, 2022, 61
DOI: 10.1002/anie.202205348

Toward Intracellular Bioconjugation Using Transition-Metal-Free Techniques

Aaditya Govindarajan and Vasuki Gnanasambandam

Bioconjugate Chem., 2021, 32, 1431
DOI: 10.1021/acs.bioconjchem.1c00173

Bis‐ethynylphosphonamidates as an Modular Conjugation Platform to Generate Multi‐Functional Protein‐ and Antibody‐Drug‐Conjugates

Marc‐André Kasper, Lukas Lassak, Annette M. Vogl, Isabelle Mai, Jonas Helma, Dominik Schumacher and Christian P. R. Hackenberger

Eur J Org Chem, 2022, 2022
DOI: 10.1002/ejoc.202101389

Ungesättigte Phosphinoxide für modulares Antikörper‐Rebridging und Einkomponenten Peptid‐Zyklisierung‐Biokonjugation

Christian E. Stieger, Alastair J. McMillan, Mark A. R. de Geus, Jan Vincent V. Arafiles, Luise Franz and Christian P. R. Hackenberger

Angewandte Chemie, 2025, 137
DOI: 10.1002/ange.202508656

Replacement of the essential nitro group by electrophilic warheads towards nitro-free antimycobacterial benzothiazinones

Héctor Torres-Gómez, François Keiff, Peter Hortschansky, Freddy Bernal, Valerie Kerndl, Florian Meyer, Nina Messerschmidt, Michael Dal Molin, Thomas Krüger, Jan Rybniker, Axel A. Brakhage and Florian Kloss

European Journal of Medicinal Chemistry, 2024, 279, 116849
DOI: 10.1016/j.ejmech.2024.116849

Synthesis and Evaluation of Non‐Hydrolyzable Phospho‐Lysine Peptide Mimics

Anett Hauser, Eleftheria Poulou, Fabian Müller, Peter Schmieder and Christian P. R. Hackenberger

Chemistry A European J, 2021, 27, 2326
DOI: 10.1002/chem.202003947

Out With a Bang: Celebrating Global Chemical Biology

Milena Schuhmacher and Sascha Hoogendoorn

ACS Chem. Biol., 2023, 18, 218
DOI: 10.1021/acschembio.2c00905

Design and Evaluation of Phosphonamidate-Linked Exatecan Constructs for Highly Loaded, Stable, and Efficacious Antibody–Drug Conjugates

Saskia Schmitt, Paul Machui, Isabelle Mai, Sarah Herterich, Swetlana Wunder, Philipp Cyprys, Marcus Gerlach, Philipp Ochtrop, Christian P.R. Hackenberger, Dominik Schumacher, Jonas Helma, Annette M. Vogl and Marc-André Kasper

Molecular Cancer Therapeutics, 2024, 23, 199
DOI: 10.1158/1535-7163.MCT-23-0359

Allenamides as a Powerful Tool to Incorporate Diversity: Thia‐Michael Lipidation of Semisynthetic Peptides and Access to β‐Keto Amides

Tae‐Ung Na, Veronika Sander, Alan J. Davidson, Rolland Lin, Yann O. Hermant, Madeleine T. Hardie Boys, Daniel Pletzer, Georgia Campbell, Scott A. Ferguson, Gregory M. Cook, Jane R. Allison, Margaret A. Brimble, Brian H. Northrop and Alan J. Cameron

Angew Chem Int Ed, 2024, 63
DOI: 10.1002/anie.202407764

Engineering Proteins for Cell Entry

Xiaoyu Feng, Ruilong Chang, Haichao Zhu, Yifan Yang, Yue Ji, Dingkang Liu, Hai Qin, Jun Yin and Haibo Rong

Mol. Pharmaceutics, 2023, 20, 4868
DOI: 10.1021/acs.molpharmaceut.3c00467

Triethylamine‐Mediated Transformation of Phosphonates into Phosphonamidates

Simon Backx, Andreas Dejaegere, Andreas Simoens, Jef Van de Poel, Dorota Krasowska, Christian V. Stevens and Sven Mangelinckx

Eur J Org Chem, 2023, 26
DOI: 10.1002/ejoc.202300172

Advances in the study of P(O)-N bond construction

Zixuan Zhang, Qiaoli Yan, Runli Gao and Hongmei Wang

Phosphorus, Sulfur, and Silicon and the Related Elements, 2023, 198, 789
DOI: 10.1080/10426507.2023.2221366

Diethynyl Phosphinates for Cysteine‐Selective Protein Labeling and Disulfide Rebridging

Christian E. Stieger, Luise Franz, Frieder Körlin and Christian P. R. Hackenberger

Angew Chem Int Ed, 2021, 60, 15359
DOI: 10.1002/anie.202100683

Ungesättigte Phosphor‐Elektrophile zur Untersuchung von Protein‐Tyrosin‐Phosphatasen

Eleftheria Poulou, Max Ruwolt, Christian E. Stieger, Kristin Kemnitz‐Hassanin and Christian P. R. Hackenberger

Angewandte Chemie, 2026, 138
DOI: 10.1002/ange.202521902

The Evolving Landscape of Antibody–Drug Conjugates: In Depth Analysis of Recent Research Progress

Janet M. Sasso, Rumiana Tenchov, Robert Bird, Kavita A. Iyer, Krittika Ralhan, Yacidzohara Rodriguez and Qiongqiong Angela Zhou

Bioconjugate Chem., 2023, 34, 1951
DOI: 10.1021/acs.bioconjchem.3c00374

Phenylpropynones as Selective Disulfide Rebridging Bioconjugation Reagents

Diederick Maes, Marvin Nicque, Mehwish Iftikhar and Johan M. Winne

Org. Lett., 2024, 26, 895
DOI: 10.1021/acs.orglett.3c04160

Cleavable Cys labeling directed Lys site-selective stapling and single-site modification

Jian Li, Qi-Long Hu, Zhendong Song, Albert S. C. Chan and Xiao-Feng Xiong

Sci. China Chem., 2022, 65, 1356
DOI: 10.1007/s11426-022-1252-7