Aminopeptidase resistant Arg-Gly-Asp analogs are stable in plasma and inhibit platelet aggregation
| Autor: | S.G. Panzer-Knodle, Kam F. Fok, Larry P. Feigen, Steven Paul Adams, Nancy S. Nicholson, Foe S. Tjoeng |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
chemistry.chemical_classification
Integrins Binding Sites Dose-Response Relationship Drug Platelet Aggregation Receptors Peptide Chemistry Molecular Sequence Data Fibrinogen Fibrinogen binding Peptide Platelet Membrane Glycoproteins Platelet membrane glycoprotein Aminopeptidases Biochemistry Aminopeptidase Platelet aggregation inhibitor Platelet Amino Acid Sequence Platelet activation Receptors Immunologic Peptide sequence Platelet Aggregation Inhibitors |
| Zdroj: | International Journal of Peptide and Protein Research. 38:124-130 |
| ISSN: | 0367-8377 |
| Popis: | Tetrapeptides containing the sequence Arg-Gly-Asp (RGD) antagonize fibrinogen binding to its platelet receptor (gp IIb/IIIa, integrin alpha IIb beta 3) and inhibit platelet aggregation in vitro. The peptides RGDS and RGDY(Me)-NH2 were rapidly degraded when incubated in human, rat, and dog plasma. HPLC analysis indicated that amino acids were sequentially removed from the peptide N-terminus, and this degradation was prevented by the aminopeptidase inhibitor bestatin. Analogs of RGDY(Me)-NH2 with an acetylated or deleted alpha-amino group were prepared. Both analogs were stable when incubated in plasma, blocked 125I-fibrinogen binding to activated platelets (IC50 = 10-30 microM) and inhibited ADP induced platelet aggregation (IC50 = 10-30 microM). This study concludes that aminopeptidase rapidly degrades RGD peptides in plasma, an important issue for in vivo testing of RGD peptides and analogs. RGD analogs intrinsically stabilized against aminopeptidase are stable in plasma and are important tools for antithrombotic studies involving antagonism of gp IIb/IIIa. |
| Databáze: | OpenAIRE |
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