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Conformational investigation of antibiotic proximicin by X-ray structure analysis and quantum studies suggest a stretched conformation of this type of γ-peptide.

Abstract : The proximicins A-C are naturally occurring cytotoxic γ-peptides that contain the unique 4-amino-furan-carboxylic acid. In contrast to the structurally related cytotoxic natural DNA binder netropsin and distamycin, both exhibiting as core building block N-methyl-4-amino-pyrrol-carboxylic acid, no DNA binding was observed for the procimicins. X-ray analysis of crystals of a protected 4-amino-furan-2-carboxylic acid dipeptide revealed a stretched conformation. In contrast, for netropsin and distamycin, sickle-shaped crystal conformations were observed. DFT-calculations elegantly confirm these conformational arrangements. The most stable conformers of the proximicins are linear whereas sickle-shaped conformations are less stable, having higher Gibbs energies. For netropsin, distamycin and the netropsin-proximicin-hybrid a sickle shaped conformation appears energetically favored. The reported results are consistent with the observations that the proximicins A-C do not bind to the DNA and have a different mode of action concerning their cytotoxic activity with respect to netropsin and distamycin.
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https://www.hal.inserm.fr/inserm-00926257
Contributor : Pierre Marquet <>
Submitted on : Thursday, January 9, 2014 - 12:08:28 PM
Last modification on : Wednesday, October 21, 2020 - 6:14:01 PM

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Alexander Denisiuk, Vivien Schubert, Falko Wolter, Elisabeth Irran, Patrick Trouillas, et al.. Conformational investigation of antibiotic proximicin by X-ray structure analysis and quantum studies suggest a stretched conformation of this type of γ-peptide.. Bioorganic and Medicinal Chemistry, Elsevier, 2013, 21 (12), pp.3582-9. ⟨10.1016/j.bmc.2013.02.051⟩. ⟨inserm-00926257⟩

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