Toward Semisynthetic Lipoproteins by Convergent Strategies Based on Click and Ligation Chemistry

摘要

Cell-membrane proteins are anchored to the lipid bilayer by single or multiple insertion of transmembrane helices or by regioselective single or dual lipidation in co-and post-transla-tional enzymatic processes,including acylation with fatty acids,prenylation,and rather commonly C-terminal amidation with glycosylphosphatidylinositols(GPI).Procedures for native and neolipidation of peptides have been comprehensively reviewed,and,more recently,even the synthesis of complex GPIs has been reported.However,lipidation of proteins at defined sites and particularly grafting of GPIs or related mimetic structures to the C termini of proteins still represent formidable long-term goals of chemistry and molecular biology.