Characterization of β‐turn and Asx‐turns mimicry in a model peptide: Stabilization via CH · · · O interaction

Abstract

The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the existence of a distinct conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees conformations, respectively, in conjunction with a gauche- disposition of the obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the newly described beta-turn- and Asx-turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essentially similar to the one perceived for a classical beta-turn and the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone torsion angles and the orientation of the central peptide bond, the overall mimicked topology resembles the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in high-resolution X-ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconventional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in peptides and proteins.

B7H6‐derived peptides trigger TNF‐α‐dependent immunostimulatory activity of lymphocytic NK92‐MI cells

“…Thus, the modified sequence 6 , TVPLN, was rationally designed to study the effect of hydrogen bonding and turn conformation on peptide binding and activity. In this case, the rationale for the exchange of the N ‐terminal Thr and Val, and replacement of the C ‐terminal Lys for Asn was based on the short peptide sequences which promoted turn conformations due to stable hydrogen‐bonding interactions with terminal Thr and Asn residues . Moreover, molecular docking studies revealed four H‐bonding interactions in between peptide 6 and the NKp30 binding site residues, Gly51 and Val53 (Figure ).…”

“…replacement of the C-terminal Lys for Asn was based on the short peptide sequences which promoted turn conformations due to stable hydrogen-bonding interactions with terminal Thr and Asn residues. 41,42 Moreover, molecular docking studies revealed four H-bonding interactions in between peptide 6 and the NKp30 binding site residues, Gly51 and Val53 ( Figure 1). The Gly51 and Val53 residues of NKp30 also contributed in H-bonding of the FG loop residues 125-130 (VTPLK) of B7-H6, found at the B7H6:NKp30 binding interface.…”

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

“….O¼ ¼C intramolecular hydrogen-bond. 28,32 In the past, Benedetti and coworkers 38 attempted to feature the importance of U-shaped molecular structures to produce rather predictable supramolecular self-assembly from enantiomeric and diastereomeric correlated peptides Boc-D AaaAaa-OMe, where Aaa may be a Leu, aIle, or Met residue. 38,39 Taken together, these studies tend to point out the propensity(ies) of terminally protected homochiral L,L and heterochiral D,L dipeptides for accommodating diverse biologically relevant folded-unfolded structures 40,41 and probably, their controlled supramolecular self-assembly.…”

“…[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.…”

DFT study of H-bonds in the peptide secondary structures: The backbone–side-chain and polar side-chains interactions

“…The first one includes the C5 conformers [2,17] of CH 3 CONHGlu-CONHCH 3 molecule. The BLYP/6-311++G** calculations have been carried out using the PC version [18] of the GAMESS(US) program package [19].…”