Compared to linear peptides, cyclic peptides have attracted much attention because of enhanced binding affinity, membrane permeability, and metabolic stability through constrained conformations. Recent studies revealed that some cyclic peptides can adopt multiple conformers, influencing their biological activity. However, strategies to control these interconversions remain underexplored. In this study, we introduced an
ortho
‐disubstituted benzamide (DiBA) unit as a molecular switch in cyclic peptides, enabling the separation of conformers and selective interconversion between four conformers. The DiBA unit has C─N and C─C bonds that can be controlled by external stimuli. The method was successfully applied to cyclic peptides with different ring sizes and amino acid sequences, and selective interconversion between conformations was achieved by different stimuli such as light and heat. These results suggest that regulating biological activity through the controlled interconversion between multiple conformations of a cyclic peptide may be applicable as a method for modulating its biological activity.
Positional isomerism, a universal structural regulation strategy in nature, achieves precise control over biological functions through minute variations in substituent positions on a molecular backbone. Despite its extensive application in small-molecule chemistry, the systematic introduction of positional isomerism as...
Cheng-Nan Yang, Guo-Quan Liu, Rui-Xue Bai et al.· ACS Macro Letters· 0 citations
Reversible covalent targeting of cysteine residues offers a powerful strategy for generating potent and tunable ligands, but designing electrophiles with balanced reactivity, stability, and reversible binding remains challenging. Here, we systematically optimized reversible α,β-unsaturated nitrile electrophiles and i...
Yu-Qian Zhang, Meng-Zhu Qi, Xian-Kai Liu et al.· Journal of the American Chem...· 0 citations
Inspired by the conformational rearrangements of G-protein-coupled receptors (GPCRs) during signal transduction in the human olfactory system, this study proposes and validates a molecular discrimination strategy based on packing mode transitions of organic supramolecular aggregates. We constructed four supramolecular...
Xiao Yang, Fei-Yu Li, Xi-Fang He et al.· Soft Matter· 0 citations
In this work, we evaluate whether computed conformational ensembles of seven tripeptides─the six C-terminal amidated D/Y/F sequence isomers and the closely related sequence FFD─are informative of their self-assembly propensity. Using all-atom molecular dynamics (AA-MD) simulations and intramolecular side-chain dihedr...
Zhuo-Jun Li, R. Ulijn, Hamish W. A. Swanson· Journal of Physical Chemistr...· 0 citations
To address the challenges posed by conformational isomerism in the sunflower trypsin inhibitor template due to proline-proline sequences in peptide design, two aptamer peptides were developed, SFTI-FGUA and SFTI-DMY, incorporating specific functional groups.
Arpan Chowdhury, Prajesh Shrestha, Vivekanandan Subramanian et al.· Journal of Enzyme Inhibition...· 0 citations
Peptide-brush polymers prepared via graft-through polymerization of peptide-based olefinic monomers form Protein-Like Polymers (PLPs) with demonstrated utility as chemical biology tools for modulating intracellular protein–protein interactions and are in development as a emerging class of therapeutic. This favorable bi...
Julia Oktawiec, Hassan Nadeem, Omar M. Ebrahim et al.· bioRxiv· 0 citations
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