دورية أكاديمية
أعرض في EDS

Synthetic antibodies block receptor binding and current-inhibiting effects of α-cobratoxin from Naja kaouthia.

التفاصيل البيبلوغرافية
العنوان: Synthetic antibodies block receptor binding and current-inhibiting effects of α-cobratoxin from Naja kaouthia.
المؤلفون: Miersch S; The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada., de la Rosa G; The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada., Friis R; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark., Ledsgaard L; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark., Boddum K; Sophion Bioscience, Ballerup, Denmark., Laustsen AH; Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark., Sidhu SS; The Donnelly Centre, University of Toronto, Toronto, Ontario, Canada.
المصدر: Protein science : a publication of the Protein Society [Protein Sci] 2022 May; Vol. 31 (5), pp. e4296.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cold Spring Harbor Laboratory Press Country of Publication: United States NLM ID: 9211750 Publication Model: Print Cited Medium: Internet ISSN: 1469-896X (Electronic) Linking ISSN: 09618368 NLM ISO Abbreviation: Protein Sci Subsets: MEDLINE
أسماء مطبوعة: Publication: 2001- : Woodbury, NY : Cold Spring Harbor Laboratory Press
Original Publication: New York, N.Y. : Cambridge University Press, c1992-
مواضيع طبية MeSH: Cobra Neurotoxin Proteins*/pharmacology , Naja naja*/metabolism, Animals ; Antivenins/pharmacology ; Horses ; Humans ; Neurotoxins/chemistry ; Neurotoxins/metabolism ; Sheep
مستخلص: Each year, thousands of people fall victim to envenomings caused by cobras. These incidents often result in death due to paralysis caused by α-neurotoxins from the three-finger toxin (3FTx) family, which are abundant in elapid venoms. Due to their small size, 3FTxs are among the snake toxins that are most poorly neutralized by current antivenoms, which are based on polyclonal antibodies of equine or ovine origin. While antivenoms have saved countless lives since their development in the late 18th century, an opportunity now exists to improve snakebite envenoming therapy via the application of new biotechnological methods, particularly by developing monoclonal antibodies against poorly neutralized α-neurotoxins. Here, we describe the use of phage-displayed synthetic antibody libraries and the development and characterization of six synthetic antibodies built on a human IgG framework and developed against α-cobratoxin - the most abundant long-chain α-neurotoxin from Naja kaouthia venom. The synthetic antibodies exhibited sub-nanomolar affinities to α-cobratoxin and neutralized the curare-mimetic effect of the toxin in vitro. These results demonstrate that phage display technology based on synthetic repertoires can be used to rapidly develop human antibodies with drug-grade potencies as inhibitors of venom toxins.
(© 2022 The Protein Society.)
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معلومات مُعتمدة: 850974 International ERC_ European Research Council
فهرسة مساهمة: Keywords: Naja kaouthia; antivenom; snake venom; synthetic antibody; α-cobratoxin
المشرفين على المادة: 0 (Antivenins)
0 (Cobra Neurotoxin Proteins)
0 (Neurotoxins)
69344-74-7 (alpha-cobratoxin)
تواريخ الأحداث: Date Created: 20220428 Date Completed: 20220502 Latest Revision: 20240826
رمز التحديث: 20240826
مُعرف محوري في PubMed: PMC8994502
DOI: 10.1002/pro.4296
PMID: 35481650
قاعدة البيانات: MEDLINE
الوصف
تدمد:1469-896X
DOI:10.1002/pro.4296