Affiliation:
1. Department of Chemical Engineering, ETS d`Enginyeria Industrial, Av. Diagonal, 647, 08028 Barcelona, Spain
Abstract
The concept of a peptidomimetic was coined about forty years ago. Since then, enormous effort
and interest have been devoted to mimic the properties of peptides with small molecules or
pseudopeptides. The present report aims to review different approaches described in the past to succeed
in this goal. Basically, there are two different approaches to design peptidomimetics: a medicinal chemistry
approach, where parts of the peptide are successively replaced by non-peptide moieties until getting
a non-peptide molecule and a biophysical approach, where a hypothesis of the bioactive form of the peptide
is sketched and peptidomimetics are designed based on hanging the appropriate chemical moieties
on diverse scaffolds. Although both approaches have been used in the past, the former has been more
widely used to design peptidomimetics of secretory peptides, whereas the latter is nowadays getting
momentum with the recent interest in designing protein-protein interaction inhibitors. The present report
summarizes the relevance of the information gathered from structure-activity studies, together with a
short review of the strategies used to design new peptide analogs and surrogates. In the following
section, there is a short discussion on the characterization of the bioactive conformation of a peptide, to
continue describing the process of designing conformationally constrained analogs producing first and
second generation peptidomimetics. Finally, there is a section devoted to reviewing the use of organic
scaffolds to design peptidomimetics based on the information available on the bioactive conformation of
the peptide.
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,General Medicine
Cited by
23 articles.
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