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Molecular Conformation and Packing of Peptide β Hairpins in the Solid State: Structures of Two Synthetic Octapeptides Containing 1‐Aminocycloalkane‐1‐Carboxylic Acid Residues at the i +2 Position of the β Turn
Author(s) -
Harini Veldore Vidya,
Aravinda Subrayashastry,
Rai Rajkishor,
Shamala Narayanaswamy,
Balaram Padmanabhan
Publication year - 2005
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200401124
Subject(s) - chemistry , molecule , peptide , hydrogen bond , monoclinic crystal system , crystallography , stereochemistry , ring (chemistry) , crystal structure , organic chemistry , biochemistry
Abstract Peptide β‐hairpin formation is facilitated by centrally positioned D ‐Pro‐Xxx segments. The synthetic peptides Boc‐Leu‐Phe‐Val‐ D ‐Pro‐Ac 6 c‐Leu‐Phe‐Val‐OMe ( 1 ) and Boc‐Leu‐Phe‐Val‐ D ‐Pro‐Ac 8 c‐Leu‐Phe‐Val‐OMe ( 2 ) were synthesized in order to explore the role of bulky 1‐aminocycloalkane‐1‐carboxylic acid residues (Ac n c, where n is the number of carbon atoms in the ring), at the i +2 position of the nucleating β turn in peptide β hairpins. Peptides 1 and 2 crystallize in the monoclinic space group P 2 1 with two molecules in the asymmetric unit. The crystal structures of 1 and 2 provide conformational parameters for four peptide hairpin molecules. In all cases, the central segments adopts a type II′ β‐turn conformation, and three of the four possible cross‐strand hydrogen bonds are observed. Fraying of the hairpins at the termini is accompanied by the observation of NH⋅⋅⋅π interaction between the Leu(1)NH group and Phe(7) aromatic group. Cross strand stabilizing interactions between the facing residues Phe(2) and Phe(7) are suggested by the observed orientation of aromatic rings. Anomalous far‐UV CD spectra observed in solution suggest that close proximity of the Phe rings is maintained even in isolated molecules. In both peptides 1 and 2 , the asymmetric unit consists of approximately orthogonal hairpins, precluding the formation of a planar β‐sheet arrangement in the solid state. Solvent molecules, one dioxane and one water in 1 , three water molecules in 2 , mediate peptide association. A comparison of molecular conformation and packing motifs in available β‐hairpin structures permits delineation of common features. The crystal structures of β‐hairpin peptides provide a means of visualizing different modes of β‐sheet packing, which may be relevant in developing models for aggregates of polypeptides implicated in disease situations.