Elucidation of the Solution Conformations of Loloatin C by NMR Spectroscopy and Molecular Simulation

Abstract

NMR experiments combined with molecular simulation with X-PLOR have been employed to determine the solution conformation of the cyclic decapeptide loloatin C in three different solutions. In DMSO, the molecule possesses a hydrophobic aromatic "wall" consisting of Trp 6 and Phe 7, and a type I β-turn structure involving Val 1, Trp 10, Asp 9 and Asn 8 with a hydrophobic head at Val 1/Trp 10 and a hydrophilic tail at Asp 9 and Asn 8; another type II' β-turn was also located between Leu 3, Tyr 4, Pro 5, and Trp 6. In 70/ 30 [D 3]TFE/H 2O, however, loloatin C possesses a dumbbell structure with all the hydrophobic side chains projecting upward on one side, forming a hydrophobic surface, and the hydrophilic side chains projecting to the other side, together with most of carbonyl oxygen atoms, thereby forming a hydrophilic surface. However, in 30:70 [D 3]TFE/H 2O, loloatin C possesses an inverse γ-turn incorporating Tyr 4, Pro 5, and Trp 6, a hydrophobic zone involving the side chains of Leu 3, Trp 6, Trp 10, and Phe 7 and a hydrophilic tail involving the hydrophilic side chains of Orn 2, Asn 8, and Asp 9. The amphiphilicity of the dumbbell structure in 70/30 [D 3]TFE/H 2O is of interest in relation to the antibiotic activity of loloatin C. © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.