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Conformational preferences of peptide–peptoid hybrid oligomers
Author(s) -
Butterfoss Glenn L.,
Drew Kevin,
Renfrew P. Douglas,
Kirshenbaum Kent,
Bonneau Richard
Publication year - 2014
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22516
Subject(s) - peptoid , chemistry , peptide , ramachandran plot , residue (chemistry) , monomer , peptidomimetic , stereochemistry , turn (biochemistry) , molecular recognition , side chain , protein structure , combinatorial chemistry , molecule , biochemistry , organic chemistry , polymer
Peptomers are oligomeric molecules composed of both α‐amino acids and N ‐substituted glycine monomers, thus creating a hybrid of peptide and peptoid units. Peptomers have been used in several applications such as antimicrobials, protease inhibitors, and antibody mimics. Despite the considerable promise of peptomers as chemically diverse molecular scaffolds, we know little about their conformational tendencies. This lack of knowledge limits the ability to implement computational approaches for peptomer design. Here we computationally evaluate the local structural propensities of the peptide–peptoid linkage. We find some general similarities between the peptide residue conformational preferences and the Ramachandran distribution of residues that precede proline in folded protein structures. However, there are notable differences. For example, several β‐turn motifs are disallowed when the i +2 residue is also a peptoid monomer. Significantly, the lowest energy geometry, when dispersion forces are accounted for, corresponds to a “ cis ‐Pro touch‐turn” conformation, an unusual turn motif that has been observed at protein catalytic centers and binding sites. The peptomer touch‐turn thus represents a useful design element for the construction of folded oligomers capable of molecular recognition and as modules in the assembly of structurally complex peptoid–protein hybrid macromolecules. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 369–378, 2014.