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从毒液中鉴定出的抗卵巢癌 Conotoxin。

Anti-Ovarian Cancer Conotoxins Identified from Venom.

机构信息

Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.

Beijing Key Laboratory of Organic Materials Testing Technology & Quality Evaluation, Institute of Analysis and Testing, Beijing Academy of Science and Technology, Beijing 100094, China.

出版信息

Molecules. 2022 Oct 5;27(19):6609. doi: 10.3390/molecules27196609.

DOI:10.3390/molecules27196609
PMID:36235146
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9573077/
Abstract

Conotoxins constitute a treasury of drug resources and have attracted widespread attention. In order to explore biological candidates from the marine cone snail, we isolated and identified three novel conopeptides named as Vi14b, Vi002, Vi003, three conotoxin variants named as Mr3d.1, Mr3e.1, Tx3a.1, and three known conotoxins (Vi15a, Mr3.8 and TCP) from crude venoms of , and Mr3.8 (I-V, II-VI, III-IV) and Tx3a.1 (I-III, II-VI, IV-V) both showed a novel pattern of disulfide connectivity, different from that previously established for the µ- and ψ-conotoxins. Concerning the effect on voltage-gated sodium channels, Mr3e.1, Mr3.8, Tx3a.1, TCP inhibited Na1.4 or Na1.8 by 21.51~24.32% of currents at semi-activated state (TP2) at 10 μmol/L. Certain anti-ovarian cancer effects on ID-8 cells were exhibited by Tx3a.1, Mr3e.1 and Vi14b with IC values of 24.29 µM, 54.97 µM and 111.6 µM, respectively. This work highlights the role of conotoxin libraries in subsequent drug discovery for ovarian cancer treatment.

摘要

芋螺毒素是药物资源的宝库，受到广泛关注。为了从海洋芋螺中探索生物候选物，我们从粗毒液中分离并鉴定了三种新型芋螺肽，分别命名为 Vi14b、Vi002 和 Vi003，三种芋螺毒素变体 Mr3d.1、Mr3e.1 和 Tx3a.1，以及三种已知的芋螺毒素（Vi15a、Mr3.8 和 TCP）。Mr3d.1（I-III，II-VI，IV-V）和 Tx3a.1（I-III，II-VI，IV-V）均表现出一种新颖的二硫键连接模式，与 µ-和 ψ-芋螺毒素之前建立的模式不同。关于对电压门控钠离子通道的影响，Mr3e.1、Mr3.8、Tx3a.1 和 TCP 在 10 μmol/L 时，在半激活状态（TP2）下，电流抑制率分别为 21.51%~24.32%。Tx3a.1、Mr3e.1 和 Vi14b 对 ID-8 细胞具有一定的抗卵巢癌作用，IC50 值分别为 24.29 μM、54.97 μM 和 111.6 μM。这项工作强调了芋螺毒素文库在随后的卵巢癌治疗药物发现中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/87a14f66535a/molecules-27-06609-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/ec42b281af91/molecules-27-06609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/8ec788693525/molecules-27-06609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/d886d47728c3/molecules-27-06609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/a929c276137d/molecules-27-06609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/708cb76c43be/molecules-27-06609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/9523cecf3260/molecules-27-06609-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/cf9cf67f45db/molecules-27-06609-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/e7a726e60340/molecules-27-06609-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/87a14f66535a/molecules-27-06609-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/ec42b281af91/molecules-27-06609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/8ec788693525/molecules-27-06609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/d886d47728c3/molecules-27-06609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/a929c276137d/molecules-27-06609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/708cb76c43be/molecules-27-06609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/9523cecf3260/molecules-27-06609-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/cf9cf67f45db/molecules-27-06609-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/e7a726e60340/molecules-27-06609-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b92/9573077/87a14f66535a/molecules-27-06609-g009.jpg

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