Synthesis of "Zinc finger'' template

Abstract

The zinc finger template brings about protein-DNA recognition. The first synthesis of a metal template which incorporates the essential features of the zinc finger motif and represented by structure(a̲) has been achieved from the key tripeptide bis-N-benzyloxycarbonyl cystinyl di-histidine methyl ester(2̲) using a novel thiol-disulfide exchange and subsequent complexation. The cobalt motif (5̲) has been similarly prepared. FAB mass spectrum 1D nmr COSY and NOESY spectra, difference NOe of (1̲) and the UV of (5̲) are in very good agreement with a ligand distribution profile around the central tetrahedral metal ion similar to that deduced for natural and synthetic zinc finger proteins. The potential of (1̲) or its appropriate variants in the understanding of diverse facets of DNA recognition is discussed. The first synthesis of template (1̲) incorporating the essential features of the zinc finger motif, has been achieved via key tripeptide, bis-Z-cystine di-his OMe using a novel thiol-disulfide exchange and complexation. Spectral studies with (1̲) and its cobalt analog show that the ligand distribution profile in (1̲) is similar to that deduced for synthetic and natural zinc finger proteins.