AI Article Synopsis
- Focal thrombus formation and vasoconstriction help protect blood vessels from damage but can become harmful if an atherosclerotic plaque ruptures.
- Researchers developed new compounds, specifically 1,4-disubstituted piperazines, that are designed to inhibit the thrombin receptor's effects without interfering with blood clotting.
- Testing showed that these compounds mimic crucial parts of thrombin receptor activating peptides and their effectiveness is linked to specific amino acid structures, enhancing understanding of their biological action.
Article Abstract
Focal thrombus formation and vasoconstriction serve to defend vessels when vascular damage occurs, but may be detrimental when an atherosclerotic plaque is disrupted. Recently, the identification of the platelet thrombin receptor opened a new area in the development of agents that may selectively inhibit the effects of thrombin on cells, without affecting fibrin formation. In this regard, we have synthesized a number of 1,4-disubstituted piperazines which are designed to be analogues of thrombin receptor activating peptides (TRAP) and carry the pharmacophoric features of Phe and Arg residues present in the active pentapeptide SFLLR. These compounds were tested in the rat aorta relaxation assay and in platelet aggregation studies and their biological activity was consistent with a direct action on thrombin receptor. Furthermore, the structure activity relationships confirmed the importance of Phe and Arg for receptor activation and the molecular modeling revealed an intriguing relationship between their amphipathic similarity with SFLLR and their biological activity.
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| http://dx.doi.org/10.1016/s0968-0896(99)00017-6 | DOI Listing |
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