Inhibition of herpesvirus ribonucleotide reductase by new synthetic peptides

ABSTRACT

The prospect of total chemical synthesis of large biologically active peptides up to the protein size has always represented a powerful tool in bioorganic chemistry. The advances made in the chemical synthesis of peptides would not have been possible without the availability of solid phase peptide synthesis [SPPS] introduced by Merrifield[1]. Since the conception of [SPPS], the chemistry developed for its application has remained fairly standardized. Like all ingenious ideas, [SPPS] also has its short-comings, for example the repetitive acidolysis required for the deprotection of [Boc] group, which may affect the acid sensitive peptide bonds and also catalyze some undesirable side reactions result in failure sequences. This initiated the development of different N-alpha-aminoblocking groups. However, the most successful one was the base labile 9-fluorenyl methoxycarbonyl Fmoc group, which is considered one of the best choices for protecting the alpha-amino-group not only because of its cleavage in weak alkaline medium [e.g. piperidine in DMF] and can therefore be used in conjunction with acid labile linker, acid sensitive amino acids and side chain protecting groups, but also because it enables- as UV active group- continuous spectroscopic monitoring during all steps of synthesis cycle[2]