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Human monoclonal scfvs that neutralize fribrinogenolytic activity of kaouthiagin, a zinc-metalloproteinase in cobra (Naja kaouthia) venom
Khanongnoi J. - ไม่ระบุหน่วยงาน
ชื่อเรื่อง (EN): Human monoclonal scfvs that neutralize fribrinogenolytic activity of kaouthiagin, a zinc-metalloproteinase in cobra (Naja kaouthia) venom
ผู้แต่ง / หัวหน้าโครงการ (EN): Khanongnoi J.
บทคัดย่อ (EN): Snake venom-metalloproteinases (SVMPs) are the primary factors that disturb hemostasis and cause hemorrhage in the venomous snake bitten subjects. Kaouthiagin is a unique SVMP that binds and cleaves von Willebrand factor (vWF) at a specific peptide bond leading to inhibition of platelet aggregation, which enhances the hemorrhage. Kaouthiagin is a low abundant venom component of Thai cobra (Naja kaouthia); thus, most horse-derived antivenins used for cobra bite treatment do not contain adequate anti-kaouthiagin. This study aimed to produce human single-chain antibody variable fragments (HuscFvs) that bind to and interfere with kaouthiagin activity for further clinical use. Kaouthiagin was purified from N. kaouthia-holovenom by a single-step gel-filtration chromatography. The purified venom component was used in phage-biopanning to select the kaouthiagin-bound HuscFv-displayed-phage clones from a HuscFv-phage display library. The selected phages were used to infect Escherichia coli bacteria. Soluble HuscFvs expressed by three phage-transformed-E. coli clones interfered with cobra kaouthiagin binding to human vWF. Computerized simulation indicated that HuscFv of two phage-transformed E. coli clones formed contact interface with kaouthiagin residues at or near catalytic site and effectively inhibited fibrinogenolytic activity of the kaouthiagin. The HuscFvs have therapeutic potential as an adjunct of antivenins in treatment of bleeding caused by venomous snakebites. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
บทคัดย่อ: ไม่พบข้อมูลจากหน่วยงานต้นทาง
ภาษา (EN): en
เอกสารแนบ (EN): https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058336274&doi=10.3390%2ftoxins10120509&partnerID=40&md5=5ceb4866d367dece09732d5c8e0724a2
เผยแพร่โดย (EN): มหาวิทยาลัยมหิดล
คำสำคัญ (EN): Western blotting
เจ้าของลิขสิทธิ์ (EN): มหาวิทยาลัยมหิดล
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Human monoclonal scfvs that neutralize fribrinogenolytic activity of kaouthiagin, a zinc-metalloproteinase in cobra (Naja kaouthia) venom
Khanongnoi J.
มหาวิทยาลัยมหิดล
ไม่ระบุวันที่เผยแพร่
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