Synthesis of Nucelopeptides by Employing an Enzyme-Labile Urethane Protecting Croup

摘要

Nucleoproteins are naturally occurring bipolymers in whcih the hydroxy group of a srine, a threonine, or a typrosine moiety is linked through a phosphodiester group to the 3'-or-5'-end of a nucleic acid. For the study of the biological phenomena in which nucleoproteins are involved, for example, viral replication, nucleopeptides embodying the characteristic linkage between the peptide chain and the oligonucleotide may serve as pwoerful tools, However, as a result of the multifunctionality and the pronounced acid and base lability of nucleopeptides, their synthesis requries the application of a variety of orthogonally stable blocking groups, which can be removed under the mildest conditions. We have developed a new mild enzymatic deprotection method, that is, the penicillin G acylase-catalyzed bydrolysis of the N-phenylacetoxybenzyloxycarboy (PhAcOZ) group, for the synthesis of nucleopeptides. We demonstrate the wide applciability of this method by coupling the N-terminally deprotected nucleopeptides 31 a-c with PhAcOZ-protected amino acids and subsequent removal of the N-PhAcOZ group from fully protected nucleotetrapeptides 32a,b with penicillin G acylase. The reaction conditions are very mild (pH 6.8) so that no undesired side reaction such as cleavage of the nucleotide bond or #beta#-elimination of the nucleotide was observed.