Synthesis of a highly hydrophobic cyclic decapeptide by solid-phase synthesis of linear peptide and cyclization in solution

A general method was described to synthesize a highly hydrophobic cyclic peptide, cyclo[LWLWLWLWLQ] where underlines indicate D-configuration of the amino acid, by a two-step solid-phase/solution synthesis strategy. The linear decapeptide was assembled by standard Boc chemistry on solid-phase and subsequently cyclized in solution with high efficiency and reproducibility. In subsequent purification by semi-preparative HPLC, 50% (v/v) DMF/H(2)O was employed as the solvent to overcome the difficulty of solubilization for the hydrophobic cyclic decapeptide and achieved a total yield of 30-35% with a purity of over 98%. (C) 2009 Wei Wu. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.