Conformational Behaviour of a Cyclolinopeptide A Analogue: Two-dimensional NMR study of cyclo(Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-ala-Val(8))(401 views) Mazzeo M, Isernia C, Rossi F, Saviano M, Pedone C, Paolillo L, Benedetti E, Pavone V
Keywords: Cyclolinopeptide A, Cyclopeptide, Solvent, Amino Acid Sequence, Article, Chemical Structure, Chemistry, Comparative Study, Nuclear Magnetic Resonance Spectroscopy, Protein Conformation, Synthesis, Thermodynamics, Models, Molecular, Molecular Structure,
Affiliations: Dipartimento di Chimica, Università di Napoli, Italy.
References: Not available.
Conformational Behaviour of a Cyclolinopeptide A Analogue: Two-dimensional NMR study of cyclo(Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-ala-Val(8))
The cyclic octapeptide cyclo[-Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-ala-Val(8-)] [C-8-Ac(6)c], containing the Pro(1)-Pro-Phe- Phe sequence, followed by a bulky helicogenic C-alpha,C-alpha-dialkylated glycine residue Ac(6)c (1-aminocyclohexane-1- carboxylic acid), and a D-Ala residue at position 7 has been synthesized. This cyclic peptide is a deletion analogue of the naturally occurring cyclic nonapeptide cyclolinopeptide A [CLA). It has been designed with the aim of studying the role that the Ac(6)c and D-Ala residues play on the conformational behaviour of the whole molecule and their influence on the conformation of the Pro(1)-Pro-Phe-Phe sequence when compared with cyclolinopeptide A. C-8-Ac(6)c has been investigated in chloroform and acetonitrile solutions by 2D NMR techniques. Only one set of sharp signals is observed in both solvents. This evidence strongly supports the hypothesis that only one conformational state exists in the chosen solvents. The interpretation of the experimental data points to the existence for C-8-Ac(6)c of a very rigid structure stabilized by intramolecular hydrogen bonds. The measured NOE effects allow the calculation of internuclear distances, which have been used as restraints in molecular dynamic calculations. The proposed conformation of the molecule shows that the Pro-Pro-Phe segment retains the conformation observed in natural CLA both in solution and in the solid state and that the Ac(6)c residue indeed reinforces the ring rigidity not permitting the formation of any appropriate cavity in which inorganic cations could be complexed.
Conformational Behaviour of a Cyclolinopeptide A Analogue: Two-dimensional NMR study of cyclo(Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-ala-Val(8))
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Conformational Behaviour of a Cyclolinopeptide A Analogue: Two-dimensional NMR study of cyclo(Pro(1)-Pro-Phe-Phe-Ac(6)c-Ile-ala-Val(8))
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