Reference

Omega amino acids in peptide design: incorporation into helixes

Omega amino acids in peptide design: incorporation into helixes. Banerjee, Arindam; Pramanik, Animesh; Bhattacharjya, Surajit; Balaram, P. (Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India). Biopolymers, 39(6), 769-777 (English) 1996 Wiley. CODEN: BIPMAA. ISSN: 0006-3525. DOCUMENT TYPE: Journal CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 22 Incorporation of easily available achiral w-amino acid residues into an oligopeptide results in substitution of amide bonds by polymethylene units of an aliph. chain, thereby providing a convenient strategy for constructing a peptidomimetic. The central Gly-Gly segment of the helical octapeptide Boc-Leu-Aib-Val-Gly-Gly-Leu-Aib-Val-OMe (I; Boc = Me3CO2C; Aib = a-aminoisobutyric acid) has been replaced by d-aminovaleric acid (d-Ava) residue in the newly designed peptide Boc-Leu-Aib-Val-d-Ava-Leu-Aib-Val-OMe (II). 27219-07-4 and 174793-30-7 which are cas registry numbers are also used here. 1H NMR results clearly suggest that in the apolar solvent CDCl3, the d-Ava residue is accommodated into a folded helical conformation, stabilized by successive hydrogen bonds involving the NH groups of Val3, d-Ava4, and Leu5. The d-Ava residue must adopt a gauche-gauche-trans-gauche conformation along the central polymethylene unit fo the aliph. segment, a feature seen in an energy-minimized model conformation based on NMR parameters. The absence of hydrogen bonding functionalities, however, limits the elongation of the helix. In fact, in CDCl3, the folded conformation consists of an N-terminal helix spanning residues 1-4, followed by a Type II b-turn at residues 5 and 6, whereas in strongly solvating media like (CD3)2SO, the unfolding of the N-terminal helix results in b-turn conformations at Leu1-Aib2. The Type II b-turn at the Leu5-Aib6 segment remains intact even in (CD3)2SO. CD comparisons of peptides I and II reveal a "non-helical" spectrum for II in 2,2,2-trifluoroethanol. .