Site-Specific PEGylation And Glycosylation Of Anti-HIV Peptide

T-20(Fuzeon(?)),being developed through the collaboration of Rache Ltd and Trimeris, Inc, is a peptide drug which used in clinical for treatment of HIV. As almost of peptide drugs, T-20 exhibits disadvantages such as short half-life-time and low stability in vivo. The aim of this dissertation is to obtain the long-acting and high stability anti-HIV peptides. With the combination of chemical and enzyamatic method, PEG and oligosaccharides were introduced into the peptides, which were synthesized with an additional cystine at the end of the non-active domain, site-specifically. Four kinds of oligosaccharides were designed and synthesized. Under the mild condition (buffer NaH2PO4/Na2HPO4 pH=7.2), Three kinds of site-specific PEGylation pepetides and two kinds of site-specific glycosylation of T-20 were successfully obtained, in the yield of 79%,82%,80%,80% and 85% respectively. Evaluation of the activity against HIV and the pharmacokinetics of the modified peptides obtained will be carried out. This research establiched a simple and efficient method of site-specific PEGylation and glycosylation of peptides, and it was also useful to dissolve the problem in the modification of peptides:(1) random chemical modification results in heterogenous products which are difficult to separate; (2) the harsh condition of modification may change the conformation of peptides.