PMID: 11916429Mar 28, 2002Paper

NMR conformational analysis of antide, a potent antagonist of the gonadotropin releasing hormone

Journal of the American Chemical Society
Giuseppe DigilioSilvio Aime

Abstract

Antide is a decapeptide [(N-Ac-D-Nal(1)-D-Cpa(2)-D-Pal(3)-Ser(4)-Lys(Nic)(5)-D-Lys(Nic)(6)-Leu(7)-Ilys(8)-Pro(9)-D-Ala(10)-NH(2)] that acts in vivo as an antagonist of GnRH (gonadotropin-releasing hormone). The conformational behavior of antide has been studied in water, TFE, DMF, and DMSO solutions by means of 2D-NMR spectroscopy and molecular dynamics calculations. Antide adopts in aqueous solution a delta-shaped backbone conformation, which is characterized by an irregular turn around residues D-Pal(3)-Ser(4) and by the close spatial proximity of the side chains belonging to D-Nal(1) and Ilys(8) (as many as 17 NOE peaks were detected between these side chains). The side-chain protons of Ilys(8) (especially the H(gamma) ones) present remarkably upfield shifted resonances, because of ring current effects induced by the naphthyl moiety. The upfield shifted resonances of the Ilys(8) H(gamma) hydrogen atoms are strictly characteristic of the water delta-shaped conformation and can be considered as structure markers. The observation of ring current shifted Ilys(8) H(gamma) resonances under different conditions (temperature, pH, solvent) indicates a remarkable stability of the water delta-shaped conformation. Such a conformation is...Continue Reading

References

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Citations

Jun 14, 2005·Biochemical and Biophysical Research Communications·J Arvid SöderhällRonald Kühne
Oct 16, 2003·Current Opinion in Pharmacology·Robert M JonesSusan Y Tamura
Dec 3, 2003·Current Opinion in Pharmacology·Karen L Herbst
Jun 9, 2005·Journal of Controlled Release : Official Journal of the Controlled Release Society·Andreas Bernkop-SchnürchChristian Huck
Apr 25, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·M D Del CurtoP Esposito
Mar 22, 2012·Contrast Media & Molecular Imaging·Concetta V GringeriSilvio Aime
May 15, 2015·Biopolymers·Anthi TapeinouTheodore Tselios

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