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Hybrid Peptide Hairpins Containing α‐ and ω‐Amino Acids: Conformational Analysis of Decapeptides with Unsubstituted β‐, γ‐, and δ‐Residues at Positions 3 and 8
Author(s) -
Roy Rituparna S.,
Gopi Hosahudya N.,
Raghothama Srinivasarao,
Karle Isabella L.,
Balaram Padmanabhan
Publication year - 2006
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.200500742
Subject(s) - peptide , chemistry , amino acid , molecule , hydrogen bond , stereochemistry , peptide conformation , crystallography , peptide sequence , circular dichroism , nuclear magnetic resonance spectroscopy , biochemistry , organic chemistry , gene
The effects of inserting unsubstituted ω‐amino acids into the strand segments of model β‐hairpin peptides was investigated by using four synthetic decapeptides, Boc‐Leu‐Val‐Xxx‐Val‐ D ‐Pro‐Gly‐Leu‐Xxx‐Val‐Val‐OMe: peptide 1 (Xxx=Gly), peptide 2 (Xxx=βGly=βhGly=homoglycine, β‐glycine), peptide 3 (Xxx=γAbu=γ‐aminobutyric acid), peptide 4 (Xxx=δAva=δ‐aminovaleric acid). 1 H NMR studies (500 MHz, methanol) reveal several critical cross‐strand NOEs, providing evidence for β‐hairpin conformations in peptides 2 – 4 . In peptide 3 , the NMR results support the formation of the nucleating turn, however, evidence for cross‐strand registry is not detected. Single‐crystal X‐ray diffraction studies of peptide 3 reveal a β‐hairpin conformation for both molecules in the crystallographic asymmetric unit, stabilized by four cross‐strand hydrogen bonds, with the γAbu residues accommodated within the strands. The D ‐Pro‐Gly segment in both molecules (A,B) adopts a type II′ β‐turn conformation. The circular dichroism spectrum for peptide 3 is characterized by a negative CD band at 229 nm, whereas for peptides 2 and 4 , the negative band is centered at 225 nm, suggesting a correlation between the orientation of the amide units in the strand segments and the observed CD pattern.