The Aggregation Properties of Some Bradykinin Analogs
| Autor: | Lajos Gera, Xiaohong Liu, John R. Cann, John M. Stewart, George Kotovych |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Magnetic Resonance Spectroscopy
Proton Protein Conformation Chemistry Stereochemistry Circular Dichroism Molecular Sequence Data Bradykinin General Medicine Peptide hormone Deuterium In vitro Structure-Activity Relationship chemistry.chemical_compound Structural Biology Yield (chemistry) Amide Molecule Amino Acid Sequence Bradykinin receptor Molecular Biology |
| Zdroj: | Journal of Biomolecular Structure and Dynamics. 11:169-179 |
| ISSN: | 1538-0254 0739-1102 |
| Popis: | Bradykinin (BK) is a peptide hormone with sequence Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9 and has been implicated in a multitude of pathophysiological processes such as the ability to lower systemic blood pressure and stimulate pain. Bulky, beta-branched D-aliphatic residues at position 7 combined with bulky L-aliphatic residues at position 8 have now been observed to yield strong antagonists. Nuclear magnetic resonance studies have been carried out on many of these molecules with a view to determining their solution conformations. However, two such analogs, namely DArg-[Hyp3, Thi5, DSer6, DCpg7, Cpg8]-BK [I] and DArg-[Hyp3, DSer6, DCpg7, Cpg8]-BK [II] (Cpg = alpha-cyclopentyl-glycine; Hyp = 4-hydroxy-L-proline, Thi = beta-(2-thienyl)-L-alanine), have exhibited an abnormal, non-linear temperature dependence for the amide NH proton of Cpg8. The NH of Arg9 also shows a slightly non-linear temperature dependence at higher temperatures above 25 degrees C. In addition, a very slow exchange rate for the NH protons of DCpg7, Cpg8 and Arg9 indicated aggregation of these two analogs, which was confirmed using the circular dichroism experiments. |
| Databáze: | OpenAIRE |
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