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Intramolecular C[BOND]H···O Hydrogen-bond mediated stabilization of a Cis-DPro imide-bond in a stereocontrolled heterochiral model peptide

Authors

  • Mohan M. Bhadbhade,

    1. Solid-State and Elemental Analysis Unit, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW 2052, Australia
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  • Raghuvansh Kishore

    Corresponding author
    1. CSIR-Institute of Microbial Technology, Protein Science and Engineering Divison, Sector 39-A, Chandigarh-160 036, India
    • CSIR-Institute of Microbial Technology, Protein Science and Engineering Divison, Sector 39-A, Chandigarh-160 036, India
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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 the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Abstract

The X-ray diffraction analysis of a stereocontrolled heterochiral designed model peptide Boc-DPro-Thr-OMe (1) revealed the existence of an unusual folded molecular structure, stabilized via an effective unconventional C[BOND]H…O type intramolecular hydrogen-bond, encompassing a noncovalent 12-membered ring-motif. Together with an uncommon type a disposition of the urethane moiety, the tightly folded topology is compounded with a cis-DPro imide-bond. The overall conformation is suggested to be the reminiscent of specific type VI β-turn structures, hitherto, characterized across the Aaa-cis-Pro peptide-bonds in globular proteins and polypeptides. The 13C NMR spectrum of 1 in an apolar CDCl3 environment revealed the presence of approximately an equal population of cis and trans isomers unexpectedly, analogous to Pro side-chain, the 13C NMR chemical-shifts of Thr Cβ-resonance is observed to be sensitive toward cis-trans isomerization. In conjunction with solid-state FT-IR spectral data, we established that a network of complex intermolecular hydrogen-bonds stabilize a self-complementary noncovalent helical hexagonal self-assembly and crystallographic supramolecular aggregate. The results incline us to highlight that the stabilization of cis-DPro peptide-bond in crystalline state may be driven by the favorable energy of formation of an unconventional weak C[BOND]H…O intramolecular hydrogen-bond. © 2011 Wiley Periodicals, Inc. Biopolymers 97: 73–82, 2012.

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