title: Intramolecular C---H···O hydrogen-bond mediated stabilization of a cis-DPro imide-bond in a stereocontrolled heterochiral model peptide.
abstract: The X-ray diffraction analysis of a stereocontrolled heterochiral designed model peptide Boc-(D) Pro-Thr-OMe (1) revealed the existence of an unusual folded molecular structure, stabilized via an effective unconventional C---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-(D) Pro 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 (13) C NMR spectrum of 1 in an apolar CDCl(3) environment revealed the presence of approximately an equal population of cis and trans isomers unexpectedly, analogous to Pro side-chain, the (13) C NMR chemical-shifts of Thr C(β) -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-(D) Pro peptide-bond in crystalline state may be driven by the favorable energy of formation of an unconventional weak C---H…O intramolecular hydrogen-bond.
authors.affiliation: Mark Wainwright Analytical Centre, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Mohan M
authors.initials: MM
authors.lastname: Bhadbhade
authors.forename: Raghuvansh
authors.initials: R
authors.lastname: Kishore
mesh_terms: D018360:Crystallography, X-Ray; D004151:Dipeptides / Q000737:chemistry*; D006860:Hydrogen Bonding; D007094:Imides / Q000737:chemistry*; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D004151:Dipeptides; D007094:Imides; D010455:Peptides; D011392:Proline