Conformational preferences of peptide–peptoid hybrid oligomers

Authors

  • Glenn L. Butterfoss,

    Corresponding author
    1. Center for Genomics and Systems Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
    • Correspondence to: Glenn Butterfoss, Center for Genomics and Systems Biology, New York University Abu Dhabi, P.O. Box 129188, Abu Dhabi, United Arab Emirates; e-mail: butter@nyu.edu

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  • Kevin Drew,

    1. Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY
    2. Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX
    Current affiliation:
    1. Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX
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  • P. Douglas Renfrew,

    1. Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY
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  • Kent Kirshenbaum,

    1. Department of Chemistry, New York University, New York, NY
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  • Richard Bonneau

    1. Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY
    2. Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, NY
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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of any preprints from the past two calendar years by emailing the Biopolymers editorial office at biopolymers@wiley.com.

ABSTRACT

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.

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