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Limiting Assumptions in the Design of Peptidomimetics
Author(s) -
Marshall Garland R.,
Ballante Flavio
Publication year - 2017
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21406
Subject(s) - peptidomimetic , limiting , computational biology , chemistry , flexibility (engineering) , combinatorial chemistry , protein design , molecular mimicry , biochemical engineering , computer science , biochemistry , protein structure , biology , engineering , peptide , genetics , mathematics , mechanical engineering , statistics , antigen
Preclinical ResearchLimiting the flexibility of organic compounds to enhance their affinity and selectivity for targeting a macromolecule involved in molecular recognition has become a well‐developed paradigm in medicinal chemistry. While the role of reverse‐turn motifs as peptidomimetics has received the most attention, β‐sheets and helices are also important motifs for protein/protein interactions. The more complicated problem of mimicking the interacting surface of noncontiguous epitopes will not be considered in this review. This limited overview focuses on efforts to use amino acid synthons as secondary‐structure mimetics as well as providing examples of peptidomimetic design focused on nonpeptide synthetic chemistry in contrast. In particular, the rationale of optimal design criteria for mimicry and the many naïve violations of those criteria made in its pursuit are emphasized. Drug Dev Res 78 : 245–267, 2017. © 2017 Wiley Periodicals, Inc.