STABLE ANALOGS OF BIOACTIVE PEPTIDES CONTAINING DISULFIDE LINKAGES

摘要

Stable analogs of cyclic peptides containing disulfide linkages are disclosed. The disulfide linkage is modified by one of four methods: (a) sulfide contraction, (b) isosteric substitution, (c) thioketal expansion, or (d) alkylation expansion. In sulfide contraction the disulfide bond (-S-S-) is replaced with a monosulfide bond (-S-) in which a bifunctional effector molecule, such as a ligand or chemotoxic agent, is bound to the new peptide linkage. In isosteric substitution, one sulfur atom is replaced with a carbon atom and at least one of the carbon atoms at the modified side is a bifuctional effector molecule. In thioketal expansion, an alkylidene unit (CR1R2-) is inserted between the two sulfur atoms. In alkylation expansion, an alkyl moiety of from C2 to C3, is inserted between the two sulfur atoms.