ISSN:
1075-2617
Keywords:
Endothelin-1
;
molecular modelling
;
solution structure
;
Chemistry
;
Biochemistry and Biotechnology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
To understand the structural requirements for the biological activity of endothelin peptides and to develop receptor selective endothelin analogues further, the solution structure of the bicyclic 21 amino acid residue vasoactive peptide, endothelin-1, has been determined in methanol-d3/water using high-resolution1H-NMR spectroscopy. To our knowledge, this solvent system has not previously been used in NMR studies of endothelin and/or endothelin-like peptides. Two-dimensional DQFCOSY, TOCSY and NOESY spectra were acquired along with a series of one-dimensional spectra. A total of 219 distance constraints and 5 angle constraints were derived from the NMR data. These were incorporated into structure calculations using distance geometry (DIANA) followed by simulated annealing and molecular dynamics. The resulting structures are characterized by an α-helical conformation, Lys9-His16, and residues Ser5-Asp8form a type I β-turn. The N-terminal region, which was not extensively constrained by NMR data, showed no preferred conformation. The C-terminal tail showed less extensive conformational averaging but no descriptive conformation could be observed. The results obtained in this study are in good agreement with previous proposals. ©1997 European Peptide Society and John Wiley & Sons, Ltd.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
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