Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2 decapeptides(518 views) Saviano G, Rossi F, Benedetti E, Pedone C, Mierke DF, Maione A, Zanotti G, Tancredi T, Saviano M
Chemistry (ISSN: 0947-6539, 1521-3765, 1521-3765electronic), 2001 Mar 16; 7(6): 1176-1183.
Keywords: Antamanide, Cyclolinopeptide A, Ion Binding, Nmr Spectroscopy, Hydrogen Bonds, Hydrophilicity, Hydrophobicity, Nuclear Magnetic Resonance Spectroscopy, Organic Solvents, Conformational Features, Complexation, Bile Salt, Calcium, Calcium Derivative, Cyclopeptide, Gramicidin S, Metal Complex, Peptide Derivative, Article, Chemical Structure, Competitive Inhibition, Complex Formation, Liver Cell, Protein Folding, Structure Activity Relation, Surface Property, Transport At The Cellular Level, Biological Transport, Models, Molecular, Molecular Conformation, Biomolecular, Structure-Activity Relationship,
Affiliations: *** IBB - CNR ***
Facoltà di Scienze MM.FF.NN., Università degli Studi del Molise, Via Mazzini 8, 86170 Isernia, Italy
Centro di Studio di Biocristallografia del C.N.R., Dipartimento di Chimica, Università di Napoli Federico II, Via Mezzocannone 4, 80134 Napoli, Italy
Department of Molecular Pharmacology, Division of Biology and Medicine, Brown University, Providence, RI 02912, United States
Centro di Chimica del Farmaco, CNR, Università di Roma la Sapienza, Piazzale A.Moro, Roma, Italy
Istituto Chimica MIB, CNR, Via Toiano 6, 80072 Arco Felice, Italy
Facolt di Scienze MM. FF. NN., Universit degli Studi del Molise, Via Mazzini 8, 86170 Isernia, Italy
References: Not available.
Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2 decapeptides
The conformational features of both free and Ca2+-complexed cyclo[Pro-Phe-Phe-Ala-Xaa]2 (with Xaa = Glu(OtBu), Lys(CIZ), Leu, and Ala) in solution have been determined by NMR spectroscopy and extensive distance-geometry calculations. The decapeptides are conformationally homogeneous in solution and show common structural features in their free and complexed forms. The structures of the free form contain only trans peptide bonds and are topologically similar to the structure of gramicidin-S, folded up in two antiparallel extended structures, stabilized by interstrand hydrogen bonds, and closed at both ends by two β-turns. In contrast, the Ca2+-complexed peptides present two cis peptide bonds and are generally similar to those observed for the metal-complexed forms of antamanide and related analogues, folded into a saddle shape with two β-turns. The Glu(OtBu)-, Leu-, and Lys(CIZ)-containing peptides examined here maintain the biological activity of the cyclolinopeptide A in their ability to competitively inhibit cholate uptake. The natural antamanide and cyclolinopeptide A are both able to inhibit the uptake of bile salts into hepatocytes. They share the same postulated active sequence Pro-Phe-Phe. Based on our structural results, we conclude that the ability to adopt a global conformation, characterized by a clear amphipathic separation of hydrophobic and hydrophilic surfaces, is an important feature for the functioning of this class of peptides.
Structural consequences of metal complexation of cyclo[Pro-Phe-Phe-Ala-Xaa]2 decapeptides