Synthesis of Thiol-FunctionalizedN-Acetylmuramyl Peptide Congeners Suitable for their Conjugation to Target Molecules

Abstract

N-Acetylmuramyl-dipeptide and tripeptide derivatives containing at the C-terminus a masked thiol function, i.e. the S-tert-butyl-thiocysteamine residue, were synthesized via thiocysteamine residue, were synthesized via direct condensation of N-acetylmuramic acid with the peptide moiety using the dicyclohexyl-carbodiimide/N-hydroxysuccinimide procedure. Reduction with tributylphosphine in aqueous organic media geerates the free thiol function for a selective conjugation of these immunomodulants with target molecules via unsymmetrical disulfide bridging with a second thiol group by the sulfenohydrazide procedure or via thioether linkage by the addition to maleimido - or aziridine-derivatives.