牛虻(中藥材名虻蟲)為專性吸血昆蟲,也是傳統(tǒng)的抗血栓中藥材,,在多種抗血栓中成藥生產(chǎn)中被用作原料,。近年來,中國(guó)科學(xué)院昆明動(dòng)物研究所賴仞研究員領(lǐng)導(dǎo)的課題組圍繞牛虻成功吸血的分子機(jī)制和發(fā)揮抗血栓的物質(zhì)基礎(chǔ)等問題對(duì)其開展了較為系統(tǒng)的研究,,從牛虻唾液腺中識(shí)別了多種功能活性蛋白或多肽(MCP 2008, 7:582-90; MCP 2009, 8:2071-9;Dev Comp Immunol 2008;32:1242-7; Toxicon 2010;55:45-51;Allergy 2011, 66:101-9),。
最近,該課題組與美國(guó)國(guó)立衛(wèi)生研究院(NIH)的Jose教授和Ivo博士合作,,從牛虻唾液腺中識(shí)別了一類新型去整合素家族蛋白,,該蛋白通過作用于膜受體aIIbb3以及aVbb從而顯著地抑制血小板聚集和抑制血管生成。
該工作提供了一類新型的抗血栓或血管生成抑制劑類抗腫瘤藥物候選分子,。
此項(xiàng)工作目前已正式發(fā)表于《血栓形成與止血》(Thrombosis and Haemostasis)(2011;105:1032-45),,研究得到了國(guó)家自然科學(xué)基金項(xiàng)目和科技部973項(xiàng)目的經(jīng)費(fèi)支持。(生物谷Bioon.com)
生物谷推薦原文出處:
Thrombosis and Haemostasis DOI: 10.1160/TH11-01-0029
A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis
D. Ma, X. Xu, S. An, H. Liu, X. Yang, J. F. Andersen, Y. Wang, F. Tokumasu, J. M. C. Ribeiro, I. M. B. Francischetti , R. Lai
A novel family of RGD-containing molecules (Tablysin-15) has been molecularly characterised from the salivary gland of the haematophagous horsefly Tabanus yao. Tablysin-15 does not share primary sequence homology to any disintegrin discovered so far, and displays an RGD motif in the N-terminus of the molecule. It is also distinct from disintegrins from Viperidae since its mature form is not released from a metalloproteinase precursor. Tablysin-15 exhibits high affinity binding for platelet αIIbβ3 and endothelial cell αVβ3 integrins, but not for α5β1 or α2β1. Accordingly, it blocks endothelial cell adhesion to vitronectin (IC50 ~1 nM) and marginally to fibronectin (IC50 ~1 μM), but not to collagen. It also inhibits fibroblast growth factor (FGF)-induced endothelial cell proliferation, and attenuates tube formation in vitro. In platelets, Tablysin-15 inhibits aggregation induced by collagen, ADP and convulxin, and prevents static platelet adhesion to immobilised fibrinogen. In addition, solid-phase assays and flow cytometry demonstrates that αIIbβ3 binds to Tablysin-15. Moreover, immobilised Tablysin-15 supports platelet adhesion by a mechanism which was blocked by anti-integrin αIIbβ3 monoclonal antibody (e.g. abciximab) or by EDTA. Furthermore, Tablysin-15 dose-dependently attenuates thrombus formation to collagen under flow. Consistent with these findings, Tablysin-15 displays antithrombotic properties in vivo suggesting that it is a useful tool to block αIIbβ3, or as a prototype to develop antithrombotics. The RGD motif in the unique sequence of Tablysin-15 represents a novel template for studying the structure-function relationship of the disintegrin family of inhibitors.