Chemical synthesis and characterization of chemokine RANTES and its analogues

RANTES, a polypeptide of 68 amino acid residues, is a member of the C-C chemokine subfamily including other monocyte chemoattractants such as MIP-1 alpha, MIP-1 beta, MCP-1, MCP-2 and MCP-3, To provide a chemically defined RANTES in quantity suitable for structure-function studies, RANTES and its analogues were synthesized, using a modified solid-phase chemistry approach. The fully protected RANTES and RANTES(3-68) were assembled by automated solid-phase methodology using Fmoc chemistry. Deprotection and cleavage of the resin bound peptides yielded crude peptides, which were then folded and further purified by reverse-phase HPLC. The chemically synthesized RANTES with its identity and purity established, was found to be immunochemically and functionally indistinguishable from the recombinant human RANTES, RANTES and its analog, RANTES(3-68), have recently been used as the substrate in the study of dipeptidyl peptidase IV (CD26)-mediated processing of RANTES and its effect on receptor specificity. (C) 1999 Academic Press.