کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8397694 | 1544165 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Conotoxin truncation as a post-translational modification to increase the pharmacological diversity within the milked venom of Conus magus
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کلمات کلیدی
HSsMBHAphenylthiohydantoinRP-HPLC/UVTriisopropylsilane9-FluorenylmethyloxycarbonylN-Terminal modificationDIEACNBrPTMsDMFFMOCpTHHYPnAChRLD50APIESI-MSDCMLC/MS - LC / MSN,N-diisopropylethylamine - N، N-دییزوپروپیلتیلامینtris(2-carboxyethyl)phosphine - tris (2-carboxyethyl) فسفینα-conotoxin - α-کانوتوکسینElectrospray Ionization Mass Spectrometry - اسپکترومتر جرم یونیزاسیون Electrospraypost-translational modification - اصلاح post-translationalcyanogen bromide - برومید سایانوژنDaltons - دالتونdimethylformamide - دی متیل فرمالیدDichloromethane - دیکلورمتانRetention time - زمان بازداریTCEP - ساکتMass spectrometry - طیف سنجی جرمیTIPS - نکاتConotoxins - کنونوکسین هاnicotinic acetylcholine receptor - گیرنده استیلکولین نیکوتینAtmospheric pressure ionization - یونیزاسیون فشار اتمسفر
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Milked venoms of Conus demonstrate direct lineage to US Food and Drug Administration approved and present in-trial drug leads. Yet the complexity of the milked venom has not been adequately investigated or characterized, in a sustainable manner. In this study we determine the extent of molecular mass differentiation in milked venom from captive Conus magus and confirm the expression of known conotoxin constituents. We demonstrate the presence of post-translational N-terminal peptide truncation, which differentiates the milked venom constituent α-conotoxin MI from the novel α-conotoxin MIC. This truncation has a direct effect on peptide bioactivity - Ki of 89.1 ± 9.1 and 248.7 ± 10.9 nM (α-conotoxin MI and MIC respectively) toward the muscle-type nAChR (Torpedo). These milked venom conotoxins demonstrated acute lethality in fish, with a LD50 of 12.24 and 23.29 μg kgâ1 for α-conotoxin MI and MIC respectively. By synthesizing and investigating the synthetic intermediate variant des[Gly]1α-conotoxin MI, it was demonstrated that retention of the N-terminal arginine residue increased affinity at the muscle-type nAChR site (binding Ki of 73.3 ± 5.8 nM and lethal toxicity level LD50 of 8.19 μg kgâ1). This post-translational modification event within the milked venom of C. magus represents a unique mechanism by which cone snails are able to increase the chemical and pharmacological diversity of their venoms.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicon - Volume 70, August 2013, Pages 170-178
Journal: Toxicon - Volume 70, August 2013, Pages 170-178
نویسندگان
Clifford A. Kapono, Parashar Thapa, Chino C. Cabalteja, Daniela Guendisch, Abby C. Collier, Jon-Paul Bingham,