由应激蛋白酶解产生的肽类物质——凯特斯汀(RSMRLSFRARGYGFR)对包括疟疾致病原恶性疟原虫在内的大量微生物具有显著的活性。通过圆二色谱、红外(衰减全反射)、高分辨率魔角旋转和宽线固态核磁共振、膜片钳和分子动力学等方法,对其作用于模拟这些微生物外部带负电荷的膜的模式进行了研究。该肽在溶液中无结构,与带负电荷的膜相互作用时会形成聚集的β折叠结构。D-凯特斯汀(D-Ctl)是从 L-凯特斯汀衍生出的一种新型环肽,其中所有 L-氨基酸均被 D-氨基酸所取代。D-Ctl 是一种强效、安全且稳定的肽类抗菌剂,未检测到耐药性。以大肠杆菌为模型,D-Ctl 目标是细菌细胞壁,导致膜通透性增加和细菌死亡。总体而言,D-Ctl 具有诸多优势,使其成为开发新型抗菌药物的理想候选药物,无论是作为单一疗法还是联合疗法,因为 D-Ctl 还具有增强多种参考抗菌药物(如头孢噻肟、阿莫西林和苯唑西林)效力的显著特性。
The peptide cateslytin (RSMRLSFRARGYGFR) produced by enzymatic degradationof stress proteins is remarkably active against a large number of microorganisms including Plasmodium Falciparum responsible for Malaria. Its mode of action on membranes mimicking the external negatively charged membrane of these microorganisms has been studied by circular dichroism, infra-red (attenuatedtotal reflection), high-resolution magic angle sample spinning and wide line solid state NMR, patch clamp and molecular dynamics. The peptide, which is unstructuredin solution, adopts an aggregated beta sheet structure upon interacting with negatively charged membranes. D-Cateslytin (D-Ctl), a new epipeptide derived from L-Cateslytin, where all L-amino acids were replaced by D-amino acids. D-Ctl emerges as a potent, safe and robust peptide antimicrobial with undetectable susceptibility to resistance. Using Escherichia coli as a model, D-Ctl targets the bacterial cell wall leading to the permeabilization of the membrane and the death of the bacteria. Overall, D-Ctl offers many assets that make it an attractive candidate for the biopharmaceutical development of new antimicrobials either as a single therapy or as a combination therapy as D-Ctl also has the remarkable property to potentiate several antimicrobials of reference such as cefotaxime, amoxicillin and methicillin.
单字母 H2N-rsmrlsfrarGyGfr-OH
多字母 H2N-DArg-DSer-DMet-DArg-DLeu-DSer-DPhe-DArg-DAla-DArg-Gly-DTyr-Gly-DPhe-DArg-OH
氨基酸个数 15
分子式 C81H130N30O19S1
平均分子量(MW) 1860.15
精确分子量(Exact Mass)(MW) 1858.98
等电点(PI) -
pH=7.0时的净电荷数 6.97
GRAVY -0.87
亲水残基比例 -
消光系数 -
溶解建议 亲水
参考文献:
Zaet A, Dartevelle P, Daouad F, et al. D-Cateslytin, a new antimicrobial peptide with therapeutic potential. Scientific Reports. 2017;7(1). doi:10.1038/s41598-017-15436-z.