Falcao Claudio Borges, Pérez-Peinado Clara, de la Torre Beatriz G, Mayol Xavier, Zamora-Carreras Héctor, Jiménez M Ángeles, Rádis-Baptista Gandhi, Andreu David
Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra , 08003 Barcelona, Spain.
Laboratory of Biochemistry and Biotechnology, Institute for Marine Sciences, Federal University of Ceará , 60455-760 Fortaleza, CE, Brazil.
J Med Chem. 2015 Nov 12;58(21):8553-63. doi: 10.1021/acs.jmedchem.5b01142. Epub 2015 Oct 26.
In silico dissection of crotalicidin (Ctn), a cathelicidin from a South American pit viper, yielded fragments Ctn[1-14] and Ctn[15-34], which were tested to ascertain to what extent they reproduced the structure and activity of the parent peptide. NMR data showing Ctn to be α-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 α-helical structure, Ctn[1-14] was totally inert toward bacteria or eukaryotic cells. In contrast, unstructured Ctn[15-34] 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[15-34] as an appealing candidate for further development as an anti-infective or antitumor lead.
对来自南美蝰蛇的一种抗菌肽——响尾蛇抗菌肽（Ctn）进行计算机模拟剖析，得到了片段Ctn[1-14]和Ctn[15-34]，对其进行测试以确定它们在多大程度上重现了母体肽的结构和活性。核磁共振数据显示Ctn在N端为α螺旋结构，在C端无结构，这些片段的类似数据与之匹配。测试了这些肽对革兰氏阳性菌和阴性菌的作用以及对肿瘤细胞和健康细胞的毒性。尽管Ctn[1-14]具有两亲性α螺旋结构，但对细菌或真核细胞完全无活性。相比之下，无结构的Ctn[15-34]重现了母体Ctn对革兰氏阴性菌和肿瘤细胞的活性，同时对真核细胞的毒性显著降低。这种对细菌和肿瘤细胞的选择性，加上其对血清的稳定性远高于Ctn，表明Ctn[15-34]是作为抗感染或抗肿瘤先导物进一步开发的有吸引力的候选物。
