title: Metallocyclopeptide complexes with MII(S.Cys)4 chromophores.
abstract: The tetracysteinyl peptide cyclo[Lys1,12](Gln-Cys-Gly-Val-Cys-Gly-Lys-Cys-Ile-Ala-Cys-Lys) ([symbol: see text] L(Cys.SH)4) was synthesized by solid-phase methods using an Fmoc/t-Bu/allyl strategy on a PAL-PEG-PS support. The formation of the 1:1 complexes with M = Fe2+, Co2+, and Ni2+ was observed by spectrophotometric monitoring of reactions in aqueous solution at pH 7.5. Size exclusion chromatography indicated that the peptide is a monomer and the complexes are dimers [M2([symbol: see text]L(Cys.S)4)2] in aqueous buffer at pH 7.5. Cobalt and nickel K-edge X-ray absorption data and EXAFS analysis of [Co2([symbol: see text] L(Cys.S)4)2] and [Ni2([symbol: see text] L(Cys.S)4)2] as lyophilized solids are reported. Derived bond distances are Co-S = 2.30 A and Ni-S = 2.21 A. From the collective results provided by absorption spectra, K-edges, EXAFS, and bond length comparisons with known structures, it is shown that [Fe2([symbol: see text] L(Cys.S)4)2] and [Co2([symbol: see text] L(Cys.S)4)2] possess distorted tetrahedral structures and [Ni2([symbol: see text] L(Cys.S)4)2] has distorted square planar stereochemistry. The Co(II) chromophore is particularly distinctive of the assigned structure, displaying three components of the parent tetrahedral ligand field transition 4A2-->4T1(P) (610, 685, 740 nm). The observed structures conform to the intrinsic stereochemical preferences of the metal ions. Structures for the binuclear complexes are suggested. These are the first characterized 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.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Nivorozhkin
authors.forename: B M
authors.initials: BM
authors.lastname: Segal
authors.forename: K B
authors.initials: KB
authors.lastname: Musgrave
authors.forename: S A
authors.initials: SA
authors.lastname: Kates
authors.forename: B
authors.initials: B
authors.lastname: Hedman
authors.forename: K O
authors.initials: KO
authors.lastname: Hodgson
authors.forename: R H
authors.initials: RH
authors.lastname: Holm
mesh_terms: D015502:Absorptiometry, Photon; D000595:Amino Acid Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D003035:Cobalt / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*; D011487:Protein Conformation
chemical_list: D010456:Peptides, Cyclic; C471985:cyclo(Lys1,12)(Gln-Cys-Gly-Val-Cys-Gly-Lys-Cys-Ile-Ala-Cys-Lys); D003035:Cobalt; D003545:Cysteine