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α – γ Hybrid Peptides that Contain the Conformationally Constrained Gabapentin Residue: Characterization of Mimetics of Chain Reversals
Author(s) -
Aravinda Subrayashastry,
Ananda Kuppanna,
Shamala Narayanaswamy,
Balaram Padmanabhan
Publication year - 2003
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.200305088
Subject(s) - hydrogen bond , dipeptide , stereochemistry , chemistry , residue (chemistry) , intramolecular force , peptide bond , peptide , side chain , amino acid , crystallography , molecule , biochemistry , organic chemistry , polymer
Abstract The crystal structures of four dipeptides that contain the stereochemically constrained γ ‐amino acid residue gabapentin (1‐(aminomethyl)cyclohexaneacetic acid Gpn) are described. The molecular conformation of Piv‐Pro‐Gpn‐OH ( 1 ), reveals a β ‐turn mimetic conformation, stabilized by a ten atom CH ⋅⋅⋅ O hydrogen bond between the Piv CO group and the pro S hydrogen of the Gpn CH 2 CO group. The peptides Boc‐Gly‐Gpn‐OH ( 2 ), Boc‐Aib‐Gpn‐OH ( 3 ), and Boc‐Aib‐Gpn‐OMe ( 4 ) form compact, folded structures, in which a distinct reversal of polypeptide chain direction is observed. In all cases, the Gpn residue adopts a gauche , gauche ( g , g ) conformation about the C γ C β ( θ 1 ) and C β C α ( θ 2 ) bonds. Two distinct Gpn conformational families are observed. In peptides 1 and 3 , the average backbone torsion angle values for the Gpn residue are ϕ =98°, θ 1 =−62°, θ 2 =−73°, and ψ =79°, while in peptide 2 and 4 the average values are ϕ =−103°, θ 1 =−46°, θ 2 =−49°, and ψ =−92°. In the case of 1 and 3 , an intramolecular nine‐membered OH ⋅⋅⋅ O hydrogen bond is formed between the CO of the preceding residue and the terminal carboxylic acid OH group. All four α – γ dipeptide sequences yield compact folded backbone conformations; this suggests that the Gpn residue may be employed successfully in the design of novel folded structures.