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Cupryphans, metal‐binding, redox‐active, redesigned conopeptides
Author(s) -
Barba Marco,
Sobolev Anatoli P.,
Romeo Cristina,
Schininà M. Eugenia,
Pietraforte Donatella,
Mannina Luisa,
Musci Giovanni,
Polticelli Fabio
Publication year - 2009
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.58
Subject(s) - chemistry , peptide , stereochemistry , active site , divalent , binding site , nuclear magnetic resonance spectroscopy , redox , dipeptide , combinatorial chemistry , biochemistry , enzyme , organic chemistry
Contryphans are bioactive peptides, isolated from the venom of marine snails of the genus Conus , which are characterized by the short length of the polypeptide chain and the high degree of unusual post‐translational modifications. The cyclization of the polypeptide chain through a single disulphide bond, the presence of two conserved Pro residues, and the epimerization of a Trp/Leu residue confer to Contryphans a stable and well‐defined structure in solution, conserved in all members of the family, and tolerant to multiple substitutions. The potential of Contryphans as scaffolds for the design of redox‐active (macro)molecules was tested by engineering a copper‐binding site on two different variants of the natural peptide Contryphan‐Vn. The binding site was designed by computational modeling, and the redesigned peptides were synthesized and characterized by optical, fluorescence, electron spin resonance, and nuclear magnetic resonance spectroscopy. The novel peptides, named Cupryphan and Arg–Cupryphan, bind Cu 2+ ions with a 1:1 stoichiometry and a K d in the 100 n M range. Other divalent metals (e.g., Zn 2+ and Mg 2+ ) are bound with much lower affinity. In addition, Cupryphans catalyze the dismutation of superoxide anions with an activity comparable to other nonpeptidic superoxide dismutase mimics. We conclude that the Contryphan motif represents a natural robust scaffold which can be engineered to perform different functions, providing additional means for the design of catalytically active mini metalloproteins.