Nonstandard amino acids in conformational design of peptides. Helical structures in crystals of 5-10 residue peptides containing dipropylglycine and dibutylglycine

Abstract

Nonstandard amino acids dipropylglycine (Dpg) and dibutylglycine (Dbg) have been incorporated into penta- to decapeptides in order to impose local restrictions on the polypeptide chain stereochemistry. In each case, the Dpg and Dbg residues showed similar helix-forming propensity as the Aib (alpha-aminoisobutyric) residue. Further, the 310- and a-helices containing the Dbg and Dpg residues had crystal packing motifs quite similar to those found for Aib-containing peptides. Crystal structure analyses are presented for Boc-Aib-Ala-Leu-Ala-Leu-Dpg-Leu-Ala-Leu-Aib-OMe (I), space group P21 with α = 11.313(3) Å, b = 28.756(5) Å, c = 11.884 Å, β = 103.74(1)"; Boc-Leu-Dpg-Leu-Ala-Leu-Aib-OMe, polymorph a (IIa), space group P1 with a = 10.205(5) Å, b = 10.996(5) Å, c = 21.393(9) Å, α = 81.92(3)", β = 88.20(3)" γ = 89.74(3)' and polymorph b (IIb), space group P212121 with a = 9.291(1) Å, b =23.003(5) Å, c = 23.085(6): and Boc-Leu-Dbg-Val-Ala-Leu-OMe (III), space group P21 with a = 9.907(2) Å, b = 16.078(3) Å, c = 13.543(3) Å, β = 104.48(2)". The observation of helical conformations at all Dpg/Dbg residues is not entirely expected on the basis of conformational energy calculations and crystal structure observations on small homooligopeptides.