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Keywords:

  • peptide design;
  • β-turn stabilization;
  • hydrophobic interactions;
  • FTIR, NMR, and CD spectroscopy

To investigate the structural role played by isostructural unbranched alkyl-chains on the conformational ensemble and stability of β-turn structures, the conformational properties of a designed model peptide: Plm-Pro-Gly-Pda (1, Plm: H3C—(CH2)14—CONH—; Pda: —CONH— (CH2)14—CH3) have been examined and compared with the parent peptide: Boc-Pro-Gly-NHMe (2, Boc: tert-butoxycarbonyl; NHMe: N-methylamide). The characteristic 13C NMR chemical-shifts of the Pro Cβ and Cγ resonances ascertained the incidence of an all-trans peptide-bond in low polarity deuterochloroform solution. Using FTIR and 1H NMR spectroscopy, we establish that apolar alkyl-chains flanking a β-turn promoting Pro-Gly sequence impart definite incremental stability to the well-defined hydrogen-bonded structure. The assessment of 1H NMR derived thermodynamic parameters of the hydrogen-bonded amide-NHs via variable temperature indicate that much weaker hydrophobic interactions do contribute to the stability of folded reverse turn structures. The far-UV CD spectral patterns of 1 and 2 in 2,2,2-trifluoroethanol are consistent with Pro-Gly specific type II β-turn structure, concomitantly substantiate that the flanking alkyl-chains induce substantial bias in enhanced β-turn populations. In view of structural as well as functional importance of the Pro-Gly mediated secondary structures, besides biochemical and biological significance of proteins lipidation via myristoylation or palmytoilation, we highlight potential convenience of the unbranched Plm and Pda moieities not only as main-chain N- and C-terminal protecting groups but also to mimic and stabilize specific isolated secondary and supersecondary structural components frequently observed in proteins and polypeptides. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 419–426, 2013.