Disintegrins from hematophagous sources
Review published in Toxins (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.
Summary
Comprehensive review of disintegrins from leeches, ticks, hookworms and other hematophagous sources; algorithm identified >450 putative sialogenins with disintegrin RGD-like motifs across hematophagous taxa.
Why This Matters for Hirudotherapy
This review examines salivary disintegrins—molecules that modulate integrin function—from hematophagous animals, noting that most have been found in tick and leech salivary glands and that the majority display RGD motifs and act as platelet aggregation inhibitors. The authors created a computational algorithm to identify putative disintegrin sequences bearing tripeptide motifs (RGD, KGD, VGD, MLD, KTS, RTS, WGD, RED) flanked by cysteines across blood-sucking species in GenBank—including leeches (Macrobdella sp., Placobdella sp.)—revealing over 450 novel candidate sequences whose biological activity remains unverified. For ASH's domain, this is relevant as it highlights the extensive diversity of bioactive anti-thrombotic molecules in leech salivary secretions. However, this is a review with computational predictions; the vast majority of identified sequences lack experimentally validated function, and leech-specific findings are embedded within a broad multi-species survey.
Citation
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