Zinc fingers, 30-residue peptides anchored on Zn(II) coordinated to pairs of cysteines and histidines, recognize DNA triplets and, as tandem modules, effect sequence read out. The focus of zinc finger-DNA interaction studies thus far has been to probe the nature of the binding of the 12-residue recognition element of the finger with DNA code bases. To understand the possible role of the Zn(II) ligand and to assess its own DNA interaction profile, [(CH) 2 Zn] (C: cysteine; H: histidine; Figure 1) was constructed from bis-t Boc-cystinyl-di-His-OMe via thiol-disulfide exchange, Zn(II) complexation, and deprotection. [(CH) 2 Zn] binds with polyd-(GrC)rpolyd(GrC) with association constants-1.8 1 10 7 M 01 (specific DNA-phosphate) and 3.3 1 10 3 M 01 (nonspecific DNA-phosphate); perturbs its B-DNA profile; and enhances the T m from 62.5 to 70.15ЊC in a concentration-independent manner, with an ideal reversal profile on cooling, not observed in the DNA alone; releases polyd(GrC)rpolyd(GrC)-bound ethidium bromide; enhances the fluorescence of polyd(GrC)rpolyd(GrC)-bound ethidium bromide at low concentrations; and quenches it at higher ranges. [(CH) 2 Zn] also binds to d ( ACGCTGGGCGT ) , the sequence associated with Zif-268, 3-finger binding site. Such interactions were not seen in parallel studies with ( a ) poly d ( ArT )rpoly d ( ArT ) and [ ( CH ) 2 Zn ] and ( b ) { [ C H 2 ] ( C : cystine; H: histidine; the direct metal-free precursor of [ ( CH ) 2 Zn ] } , ionic zinc nitrate, and covalent zinc acetyl acetonate Zn ( AcAc ) 2 , with poly [d ( GrC )rpoly d ( GrC ) ] .
The results are rationalized on the basis of two types of association between [(CH) 2 Zn] and polyd(GrC)rpolyd(GrC), a nonspecific recognition of the sugar phosphate backbone,