Convergent solid-phase approach performed in a chloroform-phenol mixed solvent:Synthesis of amyloid beta-peptides as examples with a difficult sequence

摘要

A mixture of chloroform and phenol(v/v,3/1)as a coupling medium possesses,as we demonstrated previously,the highest potential thus far known to dissolve almost all sparingly soluble protected peptides.This solvent system could be successfully applied to the synthesis of peptides with serious solubility problems in a solution employing a maximum protection strategy with Boc chemistry.In the general procedure for segment condensation reactions,excess amounts of the carboxyl components should be coupled with the amino components for completion of the reaction.However,in the case of synthesis of amyloid P-peptides(Aps)(1-40,1-42,3-42 and 1-43),the efficiency of reprecipitation to purify the desired protected peptides was extremely hampered by the remaining carboxyl components and their phenyl ester derivatives,partially generated during the coupling reaction in chloroform-phenol,due to their insolubility in ordinary organic solvents.Even after the HF procedure,contamination with these segments interfered with the purification procedure using RP-HPLC because they caused seeding of amyloid formation,resulting in a low yield of the final product.To overcome these obstacles,in the present study,we tried to employ a convergent solid-phase peptide synthesis(CSPPS)performed in chloroform-phenol for the synthesis of A beta s.