Stabilization of β‐turn conformations in enkephalins

Publisher Website
Google Scholar
Abstract
Stereochemical constraints were introduced into the enkephalin backbone by substituting .alpha.-aminoisobutyryl (Aib) residues at positions 2 and 3, instead of Gly. 1H NMR studies of Tyr-Aib-Gly-Phe-Met-NH2, Tyr-Aib-Aib-Phe-Met-NH2 and Tyr-Gly-Aib-Phe-Met-NH2 demonstrate the occurrence of folded, intramolecularly hydrogen bonded structures in organic solvents. Similar conformations are also favored in the corresponding t-butyloxycarbonyl protected tetrapeptides, which lack the Tyr residue. A .beta.-turn centered at positions 2 and 3 is proposed for the Aib2-Gly3 analog. In the Gly2-Aib3 analog, the .beta.-turn has Aib3-Phe4 as the corner residues. The Aib2-Aib3 analog adopts a consecutive .beta.-turn or 310 helical conformation. High in vivo biological activity is observed for the Aib2 and Aib2-Aib3 analogs, while the Aib3 peptide is significantly less active.