Design of a new mimochrome with unique topology(621 views) Lombardi A, Nastri F, Marasco D, Maglio O, De Sanctis G, Sinibaldi F, Santucci R, Coletta M, Pavone V
Chemistry (ISSN: 0947-6539, 1521-3765, 1521-3765electronic), 2003 Nov 21; 9(22): 5643-5654.
Keywords: Helical Structures, Heme Proteins, Miniaturized Metalloproteins, Nmr Spectroscopy, Protein Design, Characterization, Cobalt, Conformations, Isomers, Nuclear Magnetic Resonance, Spectroscopic Analysis, Stereochemistry, Synthesis (chemical), Topology, Protein Matrix, Cobalt Complex, Porphyrin Derivative, Article, Modulation, Molecular Interaction, Molecular Model, Nuclear Magnetic Resonance Spectroscopy, Protein Analysis, Protein Conformation, Stereoisomerism, Structure Analysis, Oxidation-Reduction, Peptides,
Affiliations: *** IBB - CNR ***
University of Napoli Federico II, Department of Chemistry, Complesso Univ. Monte S. Angelo, Via Cynthia, 80126 Napoli, Italy
Dept. of Molec., Cell./Anim. Biol., University of Camerino, Via F. Camerini 2, 62032 Camerino (MC), Italy
Dept. of Exp. Med. and Biochem. Sci., University of Roma Tor Vergata, Via di Tor Vergata 135, 00133 Roma, Italy
Ist. di Biostrutture e Bioimmagini, C.N.R., via Mezzocannone 6, 80134 Napoli, Italy
References: Not available.
Design of a new mimochrome with unique topology
Peptide-based metalloprotein models represent useful systems to help understand how metalloproteins can support different functions, by the use of similar metal ion cofactors. In order to shed light on the role of the protein matrix in modulating the heme properties, we developed new models: mimochromes. They are pseudo-C, symmetric systems, composed of two helical peptides covalently linked to the deuteroporphyrin. The use of C-2 symmetry is particularly advantageous, because it,simplifies the design, synthesis and characterization. However, it leaves the problem of possible diastereomeric forms. In the cobalt complex of the first derivative, mimochrome I, Lambda and Delta isomers were indeed experimentally observed. All the insights derived from the Co-III-mimochrome I structure were used to obtain a re-designed molecule, mimochrome IV. The spectroscopic characterization of the iron and cobalt derivatives suggested the presence of the Lambda isomer as unique species. The NMR solution structure of the diamagnetic Co-III-mimochrome IV confirmed the ability of the molecule to adopt a unique topology, and revealed the peptide chains to be in helical conformation, as designed. The insertion of intramolecular, inter-chain interactions was successful in favoring the formation of one of the two possible diastereomers. The stereochemically stable structure of mimochrome IV provides an attractive model for modulating the redox potential of the heme, by simple changing the peptide chain composition around the heme.