کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1358372 | 981339 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Conformational investigation of antibiotic proximicin by X-ray structure analysis and quantum studies suggest a stretched conformation of this type of γ-peptide Conformational investigation of antibiotic proximicin by X-ray structure analysis and quantum studies suggest a stretched conformation of this type of γ-peptide](/preview/png/1358372.png)
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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Journal: Bioorganic & Medicinal Chemistry - Volume 21, Issue 12, 15 June 2013, Pages 3582–3589