Design, Synthesis, and Conformational Analysis of Oligobenzanilides as Multifacial α‑Helix Mimetics

The design, synthesis, and conformational analysis of an oligobenzanilide helix mimetic scaffold capable of simultaneous mimicry of two faces of an α-helix is reported. The synthetic methodology provides access to diverse monomer building blocks amenable to solid-phase assembly in just four syntheti...

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Bibliographic Details
Published inOrganic letters Vol. 21; no. 12; pp. 4433 - 4438
Main Authors Flack, Theo, Romain, Charles, White, Andrew J. P, Haycock, Peter R, Barnard, Anna
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 21.06.2019
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Letter
Physical Sciences
Science & Technology
ROTATION
INTERFACES
PROTEIN-PROTEIN INTERACTIONS
EXPLORING KEY ORIENTATIONS
SMALL-MOLECULE INHIBITORS
AMIDE
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Summary:The design, synthesis, and conformational analysis of an oligobenzanilide helix mimetic scaffold capable of simultaneous mimicry of two faces of an α-helix is reported. The synthetic methodology provides access to diverse monomer building blocks amenable to solid-phase assembly in just four synthetic steps. The conformational flexibility of model dimers was investigated using a combination of solid and solution state methodologies supplemented with DFT calculations. The lack of noncovalent constraints allows for significant conformational plasticity in the scaffold, thus permitting it to successfully mimic residues i, i+2, i+4, i+6, i+7, and i+9 of a canonical α-helix.
Bibliography:Wellcome Trust
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ISSN:1523-7060
1523-7052
DOI:10.1021/acs.orglett.9b01115