Disintegrins from hematophagous sources
Review published in Toxins Basel (2012)
Abstract
Bloodsucking arthropods are a rich source of salivary molecules (sialogenins) which inhibit platelet aggregation, neutrophil function and angiogenesis. Here we review the literature on salivary disintegrins and their targets. Disintegrins were first discovered in snake venoms, and were instrumental in our understanding of integrin function and also for the development of anti-thrombotic drugs. In hematophagous animals, most disintegrins described so far have been discovered in the salivary gland of ticks and leeches. A limited number have also been found in hookworms and horseflies, and none identified in mosquitoes or sand flies. The vast majority of salivary disintegrins reported display a RGD motif and were described as platelet aggregation inhibitors, and few others as negative modulator of neutrophil or endothelial cell functions. This notably low number of reported disintegrins is certainly an underestimation of the actual complexity of this family of proteins in hematophagous secretions. Therefore an algorithm was created in order to identify the tripeptide motifs RGD, KGD, VGD, MLD, KTS, RTS, WGD, or RED (flanked by cysteines) in sialogenins deposited in GenBank database. The search included sequences from various blood-sucking animals such as ticks (e.g., Ixodes sp., Argas sp., Rhipicephalus sp., Amblyommasp.), tabanids (e.g., Tabanus sp.), bugs (e.g., Triatoma sp., Rhodnius prolixus), mosquitoes (e.g., Anopheles sp., Aedes sp., Culex sp.), sand flies (e.g., Lutzomyia sp., Phlebotomus sp.), leeches (e.g., Macrobdella sp., Placobdella sp.) and worms (e.g., Ancylostoma sp.). This approach allowed the identification of a remarkably high number of novel putative sialogenins with tripeptide motifs typical of disintegrins (>450 sequences) whose biological activity remains to be verified. This database is accessible online as a hyperlinked worksheet and displays biochemical, taxonomic, and gene ontology aspects for each putative disintegrin. It is also freely available for download (right click with the mouse) at links http://exon.niaid.nih.gov/transcriptome/RGD/RGD-Peps-WEB.xlsx (web version) and http://exon.niaid.nih.gov/transcriptome/RGD/RGD-sialogenins.zip (stand alone version).
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Zusammenfassung
Systematic review of disintegrins from hematophagous animals including leeches. Bioinformatic identification of 450+ putative sialogenins with RGD/KGD/MLD tripeptide motifs typical of platelet-aggregation inhibitors.
Warum dies für die Hirudotherapie relevant ist
Dieses Review untersucht Speichel-Disintegrine von hämatophagen Tieren und stellt fest, dass die meisten bisher beschriebenen aus Speicheldrüsen von Zecken und Blutegeln stammen und typischerweise RGD-Motive aufweisen, die als Thrombozytenaggregationshemmer fungieren. Die Autoren entwickelten einen Algorithmus, um GenBank nach mutmaßlichen Disintegrinen über blutsaugende Spezies hinweg – einschließlich Blutegeln wie Macrobdella sp. und Placobdella sp. – zu durchsuchen, und identifizierten über 450 neuartige Sequenzen mit charakteristischen Tripeptid-Motiven. Für den Bereich der ASH unterstreicht dies die molekulare Vielfalt des Blutegel-Sekretoms und sein Potenzial für die Entdeckung neuartiger thrombozytenhemmender oder antithrombotischer Wirkstoffe. Einschränkung: Die biologische Aktivität der überwiegenden Mehrheit der identifizierten mutmaßlichen Disintegrine bleibt unverifiziert, und aus Blutegeln stammende Sequenzen stellen nur einen Bruchteil des Gesamtdatensatzes dar.
Zitation
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