| Abstract
| - The tetracysteinyl peptide cyclo[Lys1,12](Gln-Cys-Gly-Val-Cys-Gly-Lys-Cys-Ile-Ala-Cys-Lys) (⊂L(Cys·SH)4) wassynthesized by solid-phase methods using an Fmoc/t-Bu/allyl strategy on a PAL−PEG−PS support. The formationof the 1:1 complexes with M = Fe2+, Co2+, and Ni2+ was observed by spectrophotometric monitoring of reactionsin aqueous solution at pH 7.5. Size exclusion chromatography indicated that the peptide is a monomer and thecomplexes are dimers [M2(⊂L(Cys·S)4)2] in aqueous buffer at pH 7.5. Cobalt and nickel K-edge X-ray absorptiondata and EXAFS analysis of [Co2(⊂L(Cys·S)4)2] and [Ni2(⊂L(Cys·S)4)2] as lyophilized solids are reported. Derivedbond distances are Co−S = 2.30 Å and Ni−S = 2.21 Å. From the collective results provided by absorptionspectra, K-edges, EXAFS, and bond length comparisons with known structures, it is shown that [Fe2(⊂L(Cys·S)4)2] and [Co2(⊂L(Cys·S)4)2] possess distorted tetrahedral structures and [Ni2(⊂L(Cys·S)4)2] has distorted squareplanar stereochemistry. The Co(II) chromophore is particularly distinctive of the assigned structure, displayingthree components of the parent tetrahedral ligand field transition 4A2 → 4T1(P) (610, 685, 740 nm). The observedstructures conform to the intrinsic stereochemical preferences of the metal ions. Structures for the binuclearcomplexes are suggested. These are the first characterized metal complexes of a cysteinyl cyclopeptide and amongthe few well-documented complexes of synthetic cyclopeptides. This study is a desirable first step in the designof cyclic peptides for the binding of mononuclear and polynuclear metal centers.
- The tetracysteinyl peptide cyclo[Lys1,12](Gln-Cys-Gly-Val-Cys-Gly-Lys-Cys-Ile-Ala-Cys-Lys) (⊂L(Cys·SH)4) was synthesized using solid-phase methods. Complexes between Fe(II), Co(II), and Ni(II) and the peptide with a 1:1 stoichiometry were established by spectrophotometric titrations, observed in aqueous buffer at pH 7.5. Under similar conditions, dimeric complexes [M2(⊂L(Cys·SH)4)2] were observed by size exclusion chromatography. Absorption spectra, K-edge X-ray absorption data, and EXAFS analysis demonstrate the coordination structure of the three complexes. These are among the first characterized complexes of a cysteinyl cyclopeptide.
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