An unprecedented alteration in mode of action of IsCT resulting its translocation into bacterial cytoplasm and inhibition of macromolecular syntheses.
An unprecedented alteration in mode of action of IsCT resulting its translocation into bacterial cytoplasm and inhibition of macromolecular syntheses.
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DOI：
10.1038/srep09127
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发表时间：
2015-03-16
影响因子：
4.6
通讯作者：
Ghosh JK
中科院分区：
文献类型：
--
作者：
Tripathi JK;Kathuria M;Kumar A;Mitra K;Ghosh JK
IsCT, a 13-residue, non-cell-selective antimicrobial peptide is comprised of mostly hydrophobic residues and lesser cationic residues. Assuming that placement of an additional positive charge in the non-polar face of IsCT could reduce its hydrophobic interaction, resulting in its reduction of cytotoxicity, an analog, I9K-IsCT was designed. Two more analogs, namely, E7K-IsCT and E7K,I9K-IsCT, were designed to investigate the impact of positive charges in the polar face as well as polar and non-polar faces at a time. These amino acid substitutions resulted in a significant enhancement of therapeutic potential of IsCT. IsCT and E7K-IsCT seem to target bacterial membrane for their anti-bacterial activity. However, I9K-IsCT and E7K,I9K-IsCT inhibited nucleic acid and protein syntheses in tested E. coli without perturbing its membrane. This was further supported by the observation that NBD-IsCT localized onto bacterial membrane while NBD-labeled I9K-IsCT and E7K,I9K-IsCT translocated into bacterial cytoplasm. Interestingly, IsCT and E7K-IsCT were significantly helical while I9K-IsCT and E7K,I9K-IsCT were mostly unstructured with no helix content in presence of mammalian and bacterial membrane-mimetic lipid vesicles. Altogether, the results identify two novel cell-selective analogs of IsCT with new prototype amino acid sequences that can translocate into bacterial cytoplasm without any helical structure and inhibit macromolecular syntheses.
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影响因子：
4.8
作者：
Chen, YX;Mant, CT;Hodges, RS
通讯作者：
Hodges, RS
影响因子：
19
作者：
Derossi, D;Chassaing, G;Prochiantz, A
通讯作者：
Prochiantz, A
影响因子：
4.8
作者：
Friedrich, CL;Rozek, A;Hancock, REW
通讯作者：
Hancock, REW
影响因子：
2.9
作者：
Kragol, G;Lovas, S;Otvos, L
通讯作者：
Otvos, L
DOI：
10.1046/j.1432-1033.2002.03119.x
发表时间：
2002-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Kragol, G;Hoffmann, R;Otvos, L
通讯作者：
Otvos, L