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Controlling Cyclopeptide Backbone Conformation with β/α‐Hybrid Peptide–Heterocycle Scaffolds
Author(s) -
Gentilucci Luca,
Gallo Francesca,
Meloni Fernanda,
Mastandrea Marco,
Del Secco Benedetta,
De Marco Rossella
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201600448
Subject(s) - dipeptide , chemistry , intramolecular force , rational design , hydrogen bond , peptide , template , stereochemistry , cyclic peptide , combinatorial chemistry , peptidomimetic , molecule , nanotechnology , organic chemistry , biochemistry , materials science
Cyclopeptides (CPs) have been recognized as excellent templates for the rational design of biologically active compounds. However, in the absence of constraining elements, even the small cyclotetrapeptides (CTPs) and cyclopentapeptides (CPPs) may show conformational heterogeneity, with the occurrence of mixtures of cis/trans ‐peptide bonds. In this paper, we discuss the synthesis of CTP and CPP model compounds containing 5‐aminomethyloxazolidine‐2,4‐dione (Amo)‐dipeptide scaffolds, which combine a β/α‐hybrid dipeptide structure & a Freidinger lactam‐like heterocycle. Depending on the stereochemistry, the dipeptide scaffolds were shown to efficiently promote well‐defined turn structures within the CP sequences, by taking advantage of the particular local constraints, and by establishing extra intramolecular hydrogen‐bonding interactions.