Total synthesis of bovine pancreatic ribonuclease A. Part 3. Synthesis of the protected hexapentacontapeptide ester (positions 69–124)

Abstract

Commencing with the protected hexatriacontapeptide, corresponding to the sequence of bovine pancreatic RNase A, Z(OMe)-(RNase 89–124)-OBzl, chain elongation was carried out to the hexapentacontapeptide stage, Z(OMe)-(RNase 69–124)-OBzl, by six successive azide condensations of the peptide fragments Z(OMe)-Asp-(OBzl)-Cys(MBzl)-Arg(MBS)-Glu(OBzl)-Thr-Gly-NHNH-Troc (10), Z(OMe)-Ser-Ile-Thr-NHNH₂(11), Z(OMe)-Ser-Thr-Met(O)-NHNH₂(12), Z(OMe)-Gln-Ser-Tyr-NHNH₂(13), Z(OMe)-Asn-Cys(MBzl)-Tyr-NHNH₂(14), and Z(OMe)-Gln-Thr-NHNH₂(15). The Troc group was removed from fragment (10) by treatment with Zn prior to condensation. With N-methylpyrrolidone-5% H₂O as eluant, gel-filtration on Sephacryl S-200 was employed for purification of Z(OMe)-(RNase 69–124)-OBzl which was contaminated with the acyl component used in excess during the coupling.