Metallocyclopeptide complexes with M-II(S center dot Cys)(4) chromophores

The tetracysteinyl peptide cyclo[Lys(1,12)](Gln-Cys-Gly-Val-Cys-Gly-Lys-Cys -Ile-Ala-Cys-Lys)(subset of L(Cys . SH)(4)) was synthesized by solid-phase methods using an Fmoc/t-Bu/allyl strategy on a PAL-PEG-PS support. The form ation of the 1:1 complexes with M = Fe2+, Co2+, and Ni2+ was observed by sp ectrophotomeric monitoring of reactions in aqueous solution at pH 7.5. Size exclusion chromatography indicated that the peptide is a monomer and the c omplexes are dimers [M-2(subset of L(Cys . S)(4))(2)] in aqueous buffer at pH 7.5. Cobalt and nickel K-edge X-ray absorption data and EXAFS analysis o f [Co-2(subset of L(Cy . S)(4))(2)] and [Ni-2(subset of L(Cys . S)(4))(2)] as lyophilized solids rue reported. Derived bond distances are Co-S = 2.30 Angstrom and Ni-S = 2.21 Angstrom. From the collective results provided by absorption spectra, K-edges, EXAFS, and bond length comparisons with known structures, it is shown that [Fe-2(subset of L(Cys . S)(4))(2)] and [Co-2(s ubset of L(Cys . S)(4))(2)] possess distorted tetrahedral structures and [N i-2(subset of L(Cys . S)(4))(2)] has distorted square planar stereochemistr y. The Co(TT) chromophore is particularly distinctive of the assigned struc ture, displaying three components of the parent tetrahedral ligand field tr ansition (4)A(2) --> T-4(1)(P) (610, 685, 740 nm). The observed structures conform to the intrinsic stereochemical preferences of the metal ions. Stru ctures for the binuclear complexes are suggested. These are the first chara cterized metal complexes of a cysteinyl cyclopeptide and among the few well -documented complexes of synthetic cyclopeptides. This study is a desirable first step in the design of cyclic peptides for the binding of mononuclear and polynuclear metal centers.