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

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 Trp⁶ and Phe ⁷, and a type I β-turn structure involving Val¹, Trp¹⁰, Asp⁹ and Asn⁸ with a hydrophobic head at Val¹/Trp¹⁰ and a hydrophilic tail at Asp⁹ and Asn⁸; another type II' β-turn was also located between Leu³, Tyr⁴, Pro⁵, and Trp⁶. In 70/ 30 [D₃]TFE/H₂O, 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 [D₃]TFE/H₂O, loloatin C possesses an inverse γ-turn incorporating Tyr⁴, Pro⁵, and Trp⁶, a hydrophobic zone involving the side chains of Leu³, Trp⁶, Trp¹⁰, and Phe ⁷ and a hydrophilic tail involving the hydrophilic side chains of Orn², Asn⁸, and Asp⁹. The amphiphilicity of the dumbbell structure in 70/30 [D₃]TFE/H₂O is of interest in relation to the antibiotic activity of loloatin C.