Ornatins: potent glycoprotein IIb-IIIa antagonists and platelet aggregation inhibitors from the leech Placobdella ornata
Research article published in European journal of biochemistry (1991)
Abstract
The purification and characterization of six isoforms of ornatin, potent glycoprotein IIb-IIIa (GP IIb-IIIa) antagonists and platelet aggregation inhibitors are described. These isoforms were purified from whole leech homogenates of the leech Placobdella ornata, a North American leech commonly known as the turtle leech, by trichloroacetic acid precipitation, Sephadex G-50 size exclusion chromatography, GP IIb-IIIa affinity chromatography, and C18 reverse-phase HPLC. Each of the five completely sequenced isoforms, which range from 41 to 52 residues in length, contains the Arg-Gly-Asp (RGD) sequence, a common recognition sequence in adhesion proteins, as well as 6 cysteine residues; the positions of both of these features are conserved in the primary sequences. The amino acid sequences of ornatin isoforms B, C, D, and E are highly conserved, whereas ornatin A2 and A3 are less similar and lack 9 residues at the N-terminus. The ornatins are approximately 40% identical with decorsin, a GP IIb-IIIa antagonist isolated from the leech Macrobdella decora [Seymour, J. L., Henzel, W. J., Nevins, B., Stults, J. T. & Lazarus, R. A. (1990) J. Biol. Chem. 265, 10143-10147]; furthermore, the RGD sequence and 5 out of 6 cysteine residues are maintained in the same relative positions in both decorsin and ornatin. The ornatin isoforms do not exhibit significant similarity to any members of the snake-venom-derived family of GP IIb-IIIa antagonists [Dennis, M. S., Henzel, W. J., Pitti, R. M., Lipari, M. T., Napier, M. A., Deisher, T. A., Bunting, S. & Lazarus, R. A. (1990) Proc. Natl Acad. Sci. USA 87, 2471-2475] except in the RGD region of these proteins. The ornatin isoforms inhibit the binding of GP IIb-IIIa to immobilized fibrinogen with IC50 values ranging over 2.9-5.3 nM; ornatin isoforms A2, C, and E inhibit ADP-induced human platelet aggregation with IC50 values of about 130, 280, and 440 nM, respectively.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
The purification and characterization of six isoforms of ornatin, potent glycoprotein IIb-IIIa (GP IIb-IIIa) antagonists and platelet aggregation inhibitors are described.
Por qué esto importa para la hirudoterapia
Este estudio purificó y caracterizó seis isoformas de ornatina — potentes antagonistas de la glicoproteína IIb-IIIa (GP IIb-IIIa) e inhibidores de la agregación plaquetaria — a partir de homogeneizados completos de sanguijuela de Placobdella ornata (la sanguijuela tortuga norteamericana). Las cinco isoformas completamente secuenciadas (41–52 residuos) contienen cada una un motivo RGD conservado y seis residuos de cisteína, comparten aproximadamente un 40 % de identidad con la decorsina de Macrobdella decora, e inhiben la unión de fibrinógeno a GP IIb-IIIa con valores de CI50 de 2,9–5,3 nM, y algunas isoformas seleccionadas inhiben la agregación plaquetaria humana inducida por ADP a concentraciones nanomolares a submicromolares. Esto es directamente relevante para el dominio de ASH como caracterización de compuestos antiplaquetarios bioactivos del secretoma de la sanguijuela. La advertencia honesta es que se trata de un estudio bioquímico in vitro de purificación y caracterización sin datos in vivo ni clínicos.
Citación
Ornatins: potent glycoprotein IIb-IIIa antagonists and platelet aggregation inhibitors from the leech Placobdella ornata
Mazur P et al. · European journal of biochemistry, 1991
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026