Solid state and solution conformation of [Ala7]-phalloidin: A synthetic phallotoxin analogue(593 views) Zanotti G, Falcigno L, Saviano M, D'Auria G, Bruno BM, Campanile T, Paolillo L
Keywords: Nmr Spectroscopy, Peptides, Phallotoxin Analogue, X-Ray Diffraction, Conformations, Crystal Structure, Depolymerization, Molecular Dynamics, Nuclear Magnetic Resonance, Intoxication Mechanism, Organic Compounds, Ala(7) Phalloidin, Ala(7)-Phalloidin, Alanine Derivative, Amanitin, Dimethyl Sulfoxide, F Actin, G Actin, Amanita Phalloides, Article, Chemical Structure, Mathematical Computing, Mushroom Poisoning, Nonhuman, Nuclear Magnetic Resonance Spectroscopy, Protein Secondary Structure, Solid State, Synthesis, X Ray Crystallography, X Ray Diffraction, Models, Protein Structure, Ala (7) Phalloidin, Ala (7)-Phalloidin,
Affiliations: *** IBB - CNR ***
Dipartimento di Chimica, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cintia 80126, Napoli, Italy
Centro di Chimica del Farmaco del CNR, Università di Roma La Sapienza, Piazzale A. Moro, Roma, Italy
Centro di Studio di Biocristallografia del C.N.R., Università di Napoli Federico II, Via Mezzocannone, 4 80134, Napoli, Italy
References: Not available.
Solid state and solution conformation of [Ala7]-phalloidin: A synthetic phallotoxin analogue
Phallotoxins are toxic compounds produced by poisonous mushroom Amanita phalloides and belong to the class of bicyclic peptides with a transannular thioether bridge. Their intoxication mechanism in the liver involves a specific binding of the toxins to F-actin that, consequently, prevents the depolymerization equilibrium with G-actin. Even though the conformational features of phallotoxins have been worked out in solution, the exact mechanism of interaction with F-actin is still unknown. In this study a toxic phalloidin synthetic derivative, bicyclo(Ala1-DThr2-Cys3-cis-4-hydroxy-Pro 4-Ala5-2- mercapto-Trp6-Ala7)(S-3→ 6) has been synthesized. A substitution at position 7, with an Ala residue replaces the 4,5-dihydroxy-Leu present in the natural phalloidin. This analogue has formed crystals suitable for X-ray analysis, and represents the first case for such a class of compounds. The solid-state structure as well as the solution conformation have been evaluated. NMR techniques have been used to extract interproton distances as restraints in subsequent molecular dynamics calculations. Finally, a direct comparison between structures in solution and in the solid state is presented.
Solid state and solution conformation of [Ala7]-phalloidin: A synthetic phallotoxin analogue