Conformations and mitochondrial uncoupling activity of synthetic emerimicin fragments

Several amino terminal fragments of the emerimicins (Ac-Phe1-Aib2-Aib3-Aib4-Val5-Gly6-Leu7-Aib8-Aib9-Hyp10-Gln11-D-Iva12-Hyp13-Ala/Aib14-Phol15) ranging in length from five to ten residues have been synthesized. Nuclear magnetic resonance studies have been carried out on the 1-5, 6-10, 1-6, 1-7, 1-8, 1-9, and 1-10 fragments. The number of solvent-shielded NH groups in CDCl3 solutions for 1-5, 1-6, 1-7, 1-8, 1-9, and 1-10 indicate that 310-helical structures are favored in this solvent. In (CD3)2SO, an additional NH group, assigned to Aib(3) NH is solvent exposed in the fragments longer than six residues, suggesting partial unfolding of the N-terminal β-turn or transition to an α-helical conformation. The data for fragment 6-10 are consistent with a conformation having a single Leu-Aib β-turn. Infrared studies suggest an increase in the number of intramolecular hydrogen bonds with increasing peptide chain length. Appreciable mitochondrial uncoupling activity is observed for peptides with a chain length of at least seven residues. The order of efficiencies of the fragments is 1-7 < 1-8 ~ 1-10 < 1-9, with the decapeptide exhibiting anomalously low uncoupling activity