m-aminobenzoic acid inserted beta-turn in acyclic tripeptides: a peptidomimetic design

X-ray diffraction studies show that peptides Boc-Leu-Aib-m-ABA-OMe (I) (Aib, alpha-aminoisobutyric acid; m-ABA, meta-aminobenzoic acid) and Boc-Phe-Aib-m-ABA-OMe, (II) adopt a type-II beta-turn conformation, solely stabilized by co-operative steric interactions amongst the amino acid residues. This type of U-turn without any intramolecular hydrogen bonding is generally referred to as an open turn. Although there are some examples of constrained cyclic peptides in which o-substituted benzenes have been inserted to mimic the turn region of the neurotrophin, a nerve growth factor, peptides I and II present novel two examples where m-aminobenzoic acid has been incorporated in the beta-turn of acyclic tripeptides. The result also demonstrates the first crystallographic evidence of a beta-turn structure containing an inserted m-aminobenzoic acid, which can be considered as a rigid gamma-aminobutyric acid with an all-trans extended configuration. (c) 2005 Elsevier Ltd. All rights reserved.

Peptidomimetic design of unusual turns by incorporating flexible and rigid omega-amino acids simultaneously

The tripeptides Boc-Gly-Aib-m-ABA-OMe (I), Boc-beta Ala-Aib-m-ABA-OMe (II) and Boc-gamma Abu-Aib-rn-ABA-OMe (III) (Aib: alpha-aminoisobutyric acid, beta Ala: beta-alanine, gamma Abu: gamma-aminobutyric acid, m-ABA: meta-aminobenzoic acid) with homologated amino acids at the N-terminus, the rigid gamma-amino acid m-ABA at the C-terminus and the helicogenic Aib at the central position have been chosen to create unusual turns. Single crystal X-ray diffraction studies, solvent dependent NMR titrations and 2D NMR analysis reveal that peptides II and III adopt unusual turns of 11- and 12-membered rings stabilized by modified 4 -> 1 type intramolecular hydrogen bonds. Solution phase studies indicate that peptide I exists in the beta-turn conformation stabilized by 10-membered intramolecular hydrogen bonding.