Structural Dissection of Crotalicidin, a Rattlesnake Venom Cathelicidin, Retrieves a Fragment with Antimicrobial and Antitumor Activity
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- 作者：Claudio Borges Falcao ; Clara P茅rez-Peinado ; Beatriz G. de la Torre ; Xavier Mayol ; H茅ctor Zamora-Carreras ; M. 脕ngeles Jim茅nez ; Gandhi R谩dis-Baptista ; David Andreu
- 刊名：Journal of Medicinal Chemistry
- 出版年：2015
- 出版时间：November 12, 2015
- 年：2015
- 卷：58
- 期：21
- 页码：8553-8563
- 全文大小：789K
- ISSN：1520-4804
文摘
In silico dissection of crotalicidin (Ctn), a cathelicidin from a South American pit viper, yielded fragments Ctn[1鈥?4] and Ctn[15鈥?4], which were tested to ascertain to what extent they reproduced the structure and activity of the parent peptide. NMR data showing Ctn to be 伪-helical at the N-terminus and unstructured at the C-terminus were matched by similar data from the fragments. The peptides were tested against Gram-positive and -negative bacteria and for toxicity against both tumor and healthy cells. Despite its amphipathic 伪-helical structure, Ctn[1鈥?4] was totally inert toward bacteria or eukaryotic cells. In contrast, unstructured Ctn[15鈥?4] replicated the activity of parent Ctn against Gram-negative bacteria and tumor cells while being significantly less toxic toward eukaryotic cells. This selectivity for bacteria and tumor cells, plus a stability to serum well above that of Ctn, portrays Ctn[15鈥?4] as an appealing candidate for further development as an anti-infective or antitumor lead.