Abstract：
:Protein-protein interactions are central to many biological processes, from intracellular communication to cytoskeleton assembly, and therefore represent an important class of targets for new therapeutics. The most common secondary structure in natural proteins is an α-helix. Small molecules seem to be attractive candidates for stabilizing or disrupting protein-protein interactions based on α-helices. In our study, we assessed the ability of oligopyridyl scaffolds to mimic the α-helical twist. The theoretical as well as experimental studies (X-ray diffraction and NMR) on conformations of bipyridines in the function of substituent and pyridine nitrogen positions were carried out. Furthermore, the experimental techniques showed that the conformations observed in bipyridines are maintained within a longer oligopyridyl scaffold (quaterpyridines). The alignment of the synthesized quaterpyridine with two methyl substituents showed that it is an α-helix foldamer; their methyl groups overlap very well with side chain positions, i and i + 3, of an ideal α-helix.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Santos JS,Voisin-Chiret AS,Burzicki G,Sebaoun L,Sebban M,Lohier JF,Legay R,Oulyadi H,Bureau R,Rault Sdoi
10.1021/ci200424asubject
Has Abstractpub_date
2012-02-27 00:00:00pages
429-39issue
2eissn
1549-9596issn
1549-960Xjournal_volume
52pub_type
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