pH-sensitivities of substituted orthoester model compounds for drug delivery on endocytic pathways

摘要

As models for acid-sensitive polymer-peptideconjugates, we synthesised a group of orthoester moietieslinked at one end to a diethylene glycol group and at theother end to an amino acid for subsequent linking ofbioactive peptides. Their hydrolysis rates were thenevaluated at different pH values and temperatures byNMR. The rate and extent of acid-induced hydrolysis atcritical endosomal/lysosomal pHs was heavily influencedby substituents and stereochemistry around the orthoesterring. This suggests that modifications around thisstructure may produce linkers more suitable to thedemands of the pH gradient on endocytic pathways forreleasing bioactive molecules from delivery vectors.