Krishnayan Basuroy

Structural characterization of backbone-expanded helices in hybrid peptides: (αγ)n and (αβ)n sequences with unconstrained β and γ homologues of L-Val.

Learning your I±I²I³s: The diversity of hydrogen-bonding patterns in backbone-expanded hybrid helices is shown by crystal-structure determination of several oligomeric peptides (see scheme; C=gray; H=white; O=red; N=blue). C 12 helices were observed in the I±I³ peptide series for n=2-8. In comparison, the I±I± peptide and I±I² peptide sequences show C 10 and mixed C 14/C 15 helices, respectively. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Unconstrained Homooligomeric gamma-Peptides Show High Propensity for C-14 Helix Formation

Monosubstituted γ(4)-residues (γ(4)Leu, γ(4)Ile, and γ(4)Val) form helices even in short homooligomeric sequences. C14 helix formation is established by X-ray diffraction in homooligomeric (γ)n tetra-, hexa- and decapeptide sequences demonstrating the high propensity of γ residues, with proteinogenic side chains, to adopt locally folded conformations.

C12 Helices in Long Hybrid (αγ)n Peptides Composed Entirely of Unconstrained Residues with Proteinogenic Side Chains

Unconstrained γ(4) amino acid residues derived by homologation of proteinogenic amino acids facilitate helical folding in hybrid (αγ)n sequences. The C12 helical conformation for the decapeptide, Boc-[Leu-γ(4)(R)Val]5-OMe, is established in crystals by X-ray diffraction. A regular C12 helix is demonstrated by NMR studies of the 18 residue peptide, Boc-[Leu-γ(4)(R)Val]9-OMe, and a designed 16 residue (αγ)n peptide, incorporating variable side chains. Unconstrained (αγ)n peptides show an unexpectedly high propensity for helical folding in long polypeptide sequences.

C11/C9 helices in crystals of αβ hybrid peptides and switching structures between helix types by variation in the α-residue.

Close-packed helices with mixed hydrogen bond directionality are unprecedented in the structural chemistry of α-polypeptides. While NMR studies in solution state provide strong evidence for the occurrence of mixed helices in (ββ)n and (αβ)n sequences, limited information is currently available in crystals. The peptide structures presented show the occurrence of C11/C9 helices in (αβ)n peptides. Transitions between C11 and C11/C9 helices are observed upon varying the α-amino acid residue.

Dense network of O-H ... O and C-H ... O interactions in the solid state structure of n-pentyl-2-chloro-2-deoxy-alpha-D-manno-sept 3-uloside

Single crystal X-ray structural analysis of a septanoside, namely, n-pentyl-2-chloro-2-deoxy sept-3-uloside (1) provides many finer details of the molecular structure, in addition to its preferred twist-chair conformation, namely, (5,6)TC3,4 conformation. Structural analysis reveals a dense network of O-H⋯O, C-H⋯O and van der Waals interactions that stabilize interdigitized, planar bi-layer structure of the crystal lattice.

Structural characterization of folded and extended conformations in peptides containing γ amino acids with proteinogenic side chains: crystal structures of γn, (αγ)n and γγδγ sequences

The crystal structures of nine peptides containing γ4Val and γ4Leu are described. The short sequences Boc-[γ4(R)Val]2-OMe 1, Boc-[γ4(R)Val]3-NHMe 2 and Boc-γ4(S)Val-γ4(R)Val-OMe 3 adopt extended apolar, sheet like structures. The tetrapeptide Boc-[γ4(R)Val]4-OMe 4 adopts an extended conformation, in contrast to the folded C14 helical structure determined previously for Boc-[γ4(R)Leu]4-OMe. The hybrid αγ sequence Boc-[Ala-γ4(R)Leu]2-OMe 5 adopts an S-shaped structure devoid of intramolecular hydrogen bonds, with both α residues adopting local helical conformations. In sharp contrast, the tetrapeptides Boc-[Aib-γ4(S)Leu]2-OMe 6 and Boc-[Leu-γ4(R)Leu]2-OMe 7 adopt folded structures stabilized by two successive C12 hydrogen bonds. γ4Val residues have also been incorporated into the strand segments of a crystalline octapeptide, Boc-Leu-γ4(R)Val-Val-DPro-Gly-Leu-γ4(R)Val-Val-OMe 8. The γγδγ tetrapeptide containing γ4Val and δ5Leu residues adopts an extended sheet like structure. The hydrogen bonding pattern at γ residues corresponds to an apolar sheet, while a polar sheet is observed at the lone δ residue. The transition between folded and extended structures at γ residues involves a change of the torsion angle from the gauche to the trans conformation about the Cβ–Cα bond.

Solid state structure of p-bromo phenyl 4,5,7-tri-O-benzyl-β-D-glycero-D-talo-septanoside and an analysis of non-covalent interactions.

The solid state structure of a new seven-membered sugar oxepane derivative, namely, p-bromo phenyl 4,5,7-tri-O-benzyl-β-D-glycero-D-talo-septanoside is discussed, as determined through single crystal X-ray structural determination and in relation to their conformational features. The molecule adopts twist-chair as the preferred conformation, with conformational descriptor (O,1)TC(2,3). The solid state packing of molecules is governed by a rich network of non-covalent bonding originating from O-H⋯O, C-H⋯π, C-H⋯Br and aromatic π⋯π interactions that stabilize the packing of molecules in the crystal.

Directing peptide conformation with centrally positioned pre-organized dipeptide segments: studies of a 12-residue helix and β-hairpin

Secondary structure formation in oligopeptides can be induced by short nucleating segments with a high propensity to form hydrogen bonded turn conformations. Type I/III turns facilitate helical folding while type II′/I′ turns favour hairpin formation. This principle is experimentally verified by studies of two designed dodecapeptides, Boc-Val-Phe-Leu-Phe-Val-Aib-Aib-Val-Phe-Leu-Phe-Val-OMe 1 and Boc-Val-Phe-Leu-Phe-Val-DPro-LPro-Val-Phe-Leu-Phe-Val-OMe 2. The N- and C-terminal flanking pentapeptide sequences in both cases are identical. Peptide 1 adopts a largely α-helical conformation in crystals, with a small 310 helical segment at the N-terminus. The overall helical fold is maintained in methanol solution as evidenced by NMR studies. Peptide 2 adopts an antiparallel β-hairpin conformation stabilized by 6 interstrand hydrogen bonds. Key nuclear Overhauser effects (NOEs) provide evidence for the antiparallel β-hairpin structure. Aromatic proton chemical shifts provide a clear distinction between the conformation of peptides 1 (helical) and 2 (β-hairpin). The proximity of facing aromatic residues positioned at non-hydrogen bonding positions in the hairpin results in extensively ring current shifted proton resonances in peptide 2.

Crystallographic characterization of the α,γ C12 helix in hybrid peptide sequences.

The solid‐state conformations of two αγ hybrid peptides Boc‐[Aib‐γ4(R)Ile]4‐OMe 1 and Boc‐[Aib‐γ4(R)Ile]5‐OMe 2 are described. Peptides 1 and 2 adopt C12‐helical conformations in crystals. The structure of octapeptide 1 is stabilized by six intramolecular 4 → 1 hydrogen bonds, forming 12 atom C12 motifs. The structure of peptide 2 reveals the formation of eight successive C12 hydrogen‐bonded turns. Average backbone dihedral angles for αγ C12 helices are peptide 1, Aib; φ (°) = −57.2 ± 0.8, ψ (°) = −44.5 ± 4.7; γ4(R)Ile; φ (°) = −127.3 ± 7.3, θ1 (°) = 58.5 ± 12.1, θ2 (°) = 67.6 ± 10.1, ψ (°) = −126.2 ± 16.1; peptide 2, Aib; φ (°) = −58.8 ± 5.1, ψ (°) = −40.3 ± 5.5; ψ4(R)Ile; φ (°) = −123.9 ± 2.7, θ1 (°) = 53.3 θ 4.9, θ 2 (°) = 61.2 ± 1.6, ψ (°) = −121.8 ± 5.1. The tendency of γ4‐substituted residues to adopt gauche–gauche conformations about the Cα–Cβ and Cβ–Cγ bonds facilitates helical folding. The αγ C12 helix is a backbone expanded analog of α peptide 310 helix. The hydrogen bond parameters for α peptide 310 and α‐helices are compared with those for αγ hybrid C12 helix. Copyright

CCDC 988393: Experimental Crystal Structure Determination

Related Article: Krishnayan Basuroy , Vasantham Karuppiah , and Padmanabhan Balaram|2014|Org.Lett.|16|4614|doi:10.1021/ol5021866