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[beta]-Strand Mimicry: Exploring Oligothienylpyridine Foldamers
Protein-protein interactions (PPIs) are involved in many cellular processes; consequently, the discovery of small molecules as modulators of PPIs has become an important challenge in medicinal chemistry. Structural mimetics of [alpha]-helices, [beta]-turns or [beta]-strands could maintain or restore...
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Published in: | European journal of organic chemistry 2016-12, Vol.2016 (34), p.5686 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Protein-protein interactions (PPIs) are involved in many cellular processes; consequently, the discovery of small molecules as modulators of PPIs has become an important challenge in medicinal chemistry. Structural mimetics of [alpha]-helices, [beta]-turns or [beta]-strands could maintain or restore biological functions and should possess biological activity. At this time, the most challenging classes of PPIs are those mediated by [beta]-sheet interactions, which are implicated in a number of diseases. Only a few [beta]-strand mimics have been published to date. This study presents an evaluation of oligothienylpyridyl scaffolds in view of their ability for [beta]-strand mimicry. In this study, theoretical ring twist angle predictions for these scaffolds have been validated by X-ray diffraction and molecular dynamics simulations with NMR constraints. Careful choice of substituent and heavy-atom positions in the foldamer units opens the way to produce reasonably coplanar compounds mimicking [beta]-strand side-chain distribution. |
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ISSN: | 1434-193X 1099-0690 |
DOI: | 10.1002/ejoc.201600882 |