Total synthesis of bovine pancreatic ribonuclease A. Part 1. Synthesis of the protected pentadecapeptide ester (positions 110–124)

Abstract

The main strategy for the total synthesis of bovine pancreatic ribonuclease (RNase) A is outlined with respect to deprotecting procedures and the selection of methods for the construction of the entire amino-acid sequence of this enzyme. Amino-acid derivatives bearing protecting groups removable by methanesulphonic acid were employed in combination with the TFA-labile Z(OMe) N^α-protecting group. Thirty relatively small peptide fragments were selected as the building blocks for construction of the peptide backbone. The C-terminal-protected pentadecapeptide ester, Z(OMe)-(RNase 110–124)-OBzl, was synthesized by successive condensation of three fragments, Z(OMe)-Val-His-Phe-Asp(OBzl)-Ala-Ser-Val-OBzl (1), Z(OMe)-Asn-Pro-Tyr-Val-Pro-OH (2), and Z(OMe)-Cys(MBzl)-Glu(OBzl)-Gly-OH (3).