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Themed collection The space in-between small molecules and biologicals

17 articles
Editorial

Drugs in middle space

The challenge for middle space research is to design drug molecules in synthetically accessible forms, with physical properties that permit cell membrane penetration and oral bioavailability. Image reproduced from Med. Chem. Commun., 2012, 3, 344, with permission from The Royal Society of Chemistry.

Graphical abstract: Drugs in middle space
Review Article

Crafting precise multivalent architectures

Development of elaborate three-dimensional multivalent displays appended on natural or synthetic molecular scaffolds.

Graphical abstract: Crafting precise multivalent architectures
Review Article

Emac – a comparative index for the assessment of macrocyclization efficiency

Based upon a critical analysis of macrocyclization reactions published over the last three years, a macrocyclization efficiency index, Emac, is proposed, which takes into account both yield and concentration, as a means of determining the true efficiency of a macrocyclization reaction.

Graphical abstract: Emac – a comparative index for the assessment of macrocyclization efficiency
Review Article

Informatic strategies for the discovery of polyketides and nonribosomal peptides

A modern challenge and opportunity exists for in the ability to link genomic and metabolomic data, using novel informatic methods to find new bioactive natural products.

Graphical abstract: Informatic strategies for the discovery of polyketides and nonribosomal peptides
From the themed collection: Natural Products
Review Article

Biochemical and biosynthetic preparation of natural product-like cyclic peptide libraries

Natural product gene clusters are increasingly being used to compliment biochemical methods for production of cyclic peptide libraries.

Graphical abstract: Biochemical and biosynthetic preparation of natural product-like cyclic peptide libraries
From the themed collection: Natural Products
Concise Article

Unfolded and macrocyclic ammonium derivatives of diterpenoids steviol and isosteviol having choline moieties. Synthesis and inhibitory activities toward acetylcholine- and butyrylcholinesterases

Derivatives of isosteviol and steviol possessing choline moieties have been synthesized and assayed for AchE and BchE inhibitory activity.

Graphical abstract: Unfolded and macrocyclic ammonium derivatives of diterpenoids steviol and isosteviol having choline moieties. Synthesis and inhibitory activities toward acetylcholine- and butyrylcholinesterases
Concise Article

Synthesis of precursors and macrocycle analogs of aerucyclamides as anti-trypanosomal agents

Macrocycle analogs and key fragments of aerucyclamides were obtained and evaluated against Trypanosoma brucei brucei.

Graphical abstract: Synthesis of precursors and macrocycle analogs of aerucyclamides as anti-trypanosomal agents
Concise Article

Bicycle synthesis through peptide macrocyclization using aziridine aldehydes followed by late stage disulfide bond installation

We present a method that can be applied to generate medium-sized peptidomimetic macrocycles equipped with disulfide bonds.

Graphical abstract: Bicycle synthesis through peptide macrocyclization using aziridine aldehydes followed by late stage disulfide bond installation
Concise Article

2P2Ichem: focused chemical libraries dedicated to orthosteric modulation of proteinprotein interactions

Design of focused chemical libraries dedicated to protein–protein interaction targets.

Graphical abstract: 2P2Ichem: focused chemical libraries dedicated to orthosteric modulation of protein–protein interactions
Open Access Concise Article

Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activity

First successful pseudopeptides of the KLK3-activating bicyclic peptide “C-4” are reported.

Graphical abstract: Pseudopeptides with a centrally positioned alkene-based disulphide bridge mimetic stimulate kallikrein-related peptidase 3 activity
Concise Article

Inhibition of Ras–effector interactions by cyclic peptides

Screening of a combinatorial library identified a cyclic peptide that inhibits K-Ras–effector interactions at submicromolar concentration.

Graphical abstract: Inhibition of Ras–effector interactions by cyclic peptides
Concise Article

Novel FK506 and FK520 analogues via mutasynthesis: mutasynthon scope and product characteristics

Novel FK506 and FK520 analogues were generated via biosynthetic engineering in order to generate analogue compounds with equal potency but improved pharmacological profiles compared to FK506.

Graphical abstract: Novel FK506 and FK520 analogues via mutasynthesis: mutasynthon scope and product characteristics
Concise Article

Phage display libraries of differently sized bicyclic peptides

Loop length variability in bicyclic peptide libraries increased the diversity of the motifs found in affinity selections towards the tumor-associated protease uPA.

Graphical abstract: Phage display libraries of differently sized bicyclic peptides
Concise Article

Synthesis and binding affinities for sst receptors of cyclic peptoid SRIF-mimetics

Synthesis of the first all-peptoid SRIF (Somatotropin Release-Inhibiting Factor) analogues and evaluation of their binding affinities for the five human somatostatin receptors (hsst1–5).

Graphical abstract: Synthesis and binding affinities for sst receptors of cyclic peptoid SRIF-mimetics
Concise Article

Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance

The impact of side chain functionality on the pharmacokinetics of an orally bioavailable cyclic peptide scaffold is investigated.

Graphical abstract: Optimizing PK properties of cyclic peptides: the effect of side chain substitutions on permeability and clearance
Concise Article

The solid phase supported peptide synthesis of analogues of the lantibiotic lactocin S

Four analogues of lactocin S, an antimicrobial lantibiotic peptide produced by Lactobacillus sakei L45, have been generated using solid phase peptide synthesis. These compounds show enhanced oxidative stability to atmospheric oxygen and provide information on structure–activity relationships.

Graphical abstract: The solid phase supported peptide synthesis of analogues of the lantibiotic lactocin S
From the themed collection: Natural Products
Concise Article

Unprecedented inhibition of resistant penicillin binding proteins by bis-2-oxoazetidinyl macrocycles

Bis-2-oxoazetidinyl macrocycles, obtained as unexpected products of RCM cyclizations, exhibit good activities against D,D-peptidase from Actinomadura R39 and revealed very promising activities against PBP2a from methicillin-resistant Staphylococcus aureus.

Graphical abstract: Unprecedented inhibition of resistant penicillin binding proteins by bis-2-oxoazetidinyl macrocycles
17 articles

About this collection

MedChemComm is delighted to publish a collection of articles covering important findings and advances in the field of non-traditional drug molecules that occupy the ‘middle space’ between ‘Rule of 5’ compliant small molecules and biologicals.

The collection, guest edited by Drs Nick Terrett (Ensemble Therapeutics) and David Rees (Astex Pharmaceuticals), will include the design, synthesis, optimization, modelling, analysis and profiling of peptides, peptidomimetics, macrocycles, natural products, natural product mimetics, and any other molecule in range of approximately 500 to 3000 Daltons.

Articles in this collection will be added below as soon as possible after they are published.

Please return to this page frequently to see the collection grow.

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