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响尾蛇蛇毒中阳离子肽——克他命的生物学多样性。

Biological versatility of crotamine--a cationic peptide from the venom of a South American rattlesnake.

机构信息

Laboratório de Genética e Laboratório Especial de Toxinologia Aplicada - CAT/CEPID do Instituto Butantan, Av. Vital Brazil 1500, 05503-900, São Paulo, SP, Brasil.

出版信息

Expert Opin Investig Drugs. 2010 Dec;19(12):1515-25. doi: 10.1517/13543784.2010.534457. Epub 2010 Nov 10.

Abstract

IMPORTANCE OF THE FIELD

Molecules isolated from animals, insects, plants or microorganisms can provide prototypes for design of biopharmaceutical products. Some venom toxins and their derivatives are used in medicine, while others provide templates for development of new drugs.

AREAS COVERED IN THIS REVIEW

The mild toxin, crotamine, a small basic low-molecular-weight polypeptide purified from the venom of a South American rattlesnake, Crotalus durissus terrificus. Crotamine was discovered more than 50 years ago and only in the past six years has its exceptional biological versatility been demonstrated. Particularly, its cell-penetrating ability, which allows crotamine to cross cell membranes and to accumulate in the nucleus; its use for intracellular vesicle tracking and as a cell cycle marker and its capability for delivering DNA into replicating mammalian cells. Both antimicrobial action and potential selective antitumor activity of crotamine have also been found.

WHAT THE READER WILL GAIN

Multidisciplinary approaches and pathways of discovery placed crotamine in a rare category of versatile biomolecules, in which concentration, molecular target preference, structural ancestry and specificity toward biological membranes play an integral role.

TAKE HOME MESSAGE

Crotamine is a druggable peptide with high potential for use as an imaging agent for detecting dividing cells, for intracellular delivery of hydrophilic biomolecules, and as an alternative chemotherapeutic compound against aggressive types of cancer.

摘要

重要性领域

从动物、昆虫、植物或微生物中分离出的分子可以为生物制药产品的设计提供原型。一些毒液毒素及其衍生物在医学中得到应用,而另一些则为开发新药提供了模板。

本篇综述涵盖内容

从南美响尾蛇 Crotalus durissus terrificus 的毒液中分离得到的一种温和毒素——crotamine。crotamine 是一种碱性小分子低分子量多肽,它被发现于 50 多年前,直到最近六年,其非凡的生物学多功能性才得以证明。特别是它的细胞穿透能力,使 crotamine 能够穿过细胞膜并在核内积累;它可用于细胞内囊泡追踪和作为细胞周期标记,以及将 DNA 递送至复制的哺乳动物细胞的能力。crotamine 还具有抗菌作用和潜在的选择性抗肿瘤活性。

读者将获得

多学科的方法和发现途径使 crotamine 成为一种罕见的多功能生物分子,其浓度、分子靶标偏好、结构起源和对生物膜的特异性起着至关重要的作用。

结论

crotamine 是一种可成药的肽,具有作为检测分裂细胞的成像剂、亲水性生物分子的细胞内递药以及作为对抗侵袭性癌症的替代化学治疗化合物的高潜力。

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