Crystallographically observed folded topology of an unsubstituted γ‐aminobutyric acid incorporated in a model peptide: Importance of a CH···O interaction

Abstract

To validate the existing hypothesis put forward by Navarro et al., we performed single crystal X-ray diffraction structural analysis of a designed model peptide incorporating an unsubstituted achiral γ-aminobutyric acid: Boc-Pro-γ-Abu-OH (1) lacking C-terminal amide group. The analysis established existence of an overall unusual tightly folded topology stabilized by a conventional N(i)···H--N(i + 1) and an unconventional C(i)--H···O(i) type intramolecular hydrogen bonding interactions, encompassing a five-membered and a six-membered ring motifs, respectively. Moreover, in conjunction with Fourier transform infrared (FT-IR) absorption study in solid KBr, the results provided evidence that two conventional and one unconventional noncovalent intermolecular interaction stabilize a right-handed helical architecture generated via molecular self-assembly by translating the symmetry related molecules along the crystallographic b axis. © 2010 Wiley Periodicals, Inc. Biopolymers 93: 927-931, 2010.

Intramolecular CH···O Hydrogen‐bond mediated stabilization of a Cis‐DPro imide‐bond in a stereocontrolled heterochiral model peptide

“…[56][57][58][59][60] As shown in Figure 4, the observed FT-IR spectrum of the crystalline sample 1 in KBr disc displays intense absorption bands at $3435 and 3314 cm 21 in amide-A region and at $1745, 1676, and 1662 cm 21 in amide-I region. 33,58,59 The fact that molecular conformation of 1 is devoid of a conventional intramolecular hydrogen-bond, the appearance of two intense peaks in amide-A region may indicate the involvement of Thr O c H and amide-NH donor groups in strong intermolecular interactions. [56][57][58][59][60] The presence of a deep carbonyl absorption at $1745 cm 21 in amide-I region may be ascribed to the methyl ester participating in hydrogen-bonding interactions.…”

“…[45][46][47] In short peptides, the cis and trans peptide-bonds can exhibit marked influence on the overall preferred molecular structure and consequently, their shapespecific supramolecular self-assemblies. 33 Unexpectedly, the …”

“…[16][17][18][19][20][21][22][23][24][25][26] peptide chain reversal at the C-terminus of helical segments terminating in 'Schellma-motif. 32,33 As one of our series of investigations, we have been involved in designing biologically relevant unusual foldedunfolded structural features in Thr containing homochiral or heterochiral model peptides of the type Boc-Aaa-Thr-OMe, where Aaa may be a proteinogenic or nonproteinogenic a-amino acid. 28,32,[34][35][36][37] We previously reported, using X-ray diffraction analysis and 1 H NMR spectroscopy, the characterization of a novel Asx-turns like motif in terminally blocked homochiral peptides Boc-Thr-Thr-OMe and Boc-Thr-Thr-NH 2 , stabilized by an unconventional main-chain to sidechain C c À ÀH.…”

Unusual Folding Propensity of an Unsubstituted β,γ‐Hybrid Model Peptide: Importance of the CH⋅⋅⋅O Intramolecular Hydrogen Bond

“…j On the other hand, under these conditions, γ‐Abu exhibits strong bias for folded gauche ( θ 1 and/or θ 2 ∼±60±20°) dispositions 2. In fact, we recently demonstrated that even in the absence of a C‐terminal amide group, γ‐Abu, that is, the CONH(CH 2 ) 3 COOH moiety, adopted a folded conformation 2g. The existing literature inclined us to suggest that experimental characterisation of a fully‐extended γ‐Abu residue, that is, ϕ ≈ θ 1 ≈ θ 2 ≈ ψ ≈±180±20° conformation, could be rather demanding 2g.…”

“…In fact, we recently demonstrated that even in the absence of a C‐terminal amide group, γ‐Abu, that is, the CONH(CH 2 ) 3 COOH moiety, adopted a folded conformation 2g. The existing literature inclined us to suggest that experimental characterisation of a fully‐extended γ‐Abu residue, that is, ϕ ≈ θ 1 ≈ θ 2 ≈ ψ ≈±180±20° conformation, could be rather demanding 2g. We believe that subtle modulation of folded structural features by inserting limited methylene units through β‐Ala and/or γ‐Abu residue(s) in appositely designed peptides could be constructive for expanding the range of accessible secondary structural components 1.…”