1. Structure-activity relationship of potent antimicrobial peptide analogs of Ixosin-B amide
Yu-Shan Wu, Zih-Jie Liao, Kai-Shiuan Wang, Feng-Di T Lung Bioorg Med Chem Lett. 2013 May 15;23(10):2929-32. doi: 10.1016/j.bmcl.2013.03.053. Epub 2013 Mar 25.
There is a great urgency in developing a new generation of antibiotics and antimicrobial agents since the bacterial resistance to antibiotics have increased dramatically. A series of overlapped peptide fragments of Ixosin-B, an antimicrobial peptide with amino acid sequence of QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY, was designed, synthesized and examined for their antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A potent 11-mer peptide TSG-8-1, WWSYVRRWRSR-amide, was developed, which exhibited antimicrobial activity against E. coli and S. aureus while very little hemolytic activity in human erythrocytes was observed at high dose level. This peptide could be further modified for the development of a potent antimicrobial agent in the future.
2. Anticancer activities of an antimicrobial peptide derivative of Ixosin-B amide
Yu-Cheng Hsiao, Kai-Shiuan Wang, Shu-Huai Tsai, Wei-Ting Chao, Feng-Di T Lung Bioorg Med Chem Lett. 2013 Oct 15;23(20):5744-7. doi: 10.1016/j.bmcl.2013.07.063. Epub 2013 Aug 9.
In nature, antimicrobial peptides (AMPs) represent the first line of defense against infection by pathogens; thus, they are generally good candidates for the development of antimicrobial agents. Recently, we reported two potent antimicrobial peptides, KWLRRVWRWWR-amide (MAP-04-03) and KRLRRVWRRWR-amide (MAP-04-04), which were derived from a fragment of Ixosin-B-amide (KSDVRRWRSRY). Since some cationic AMPs exhibited cytotoxic activity against cancer cells, in the current study, we further investigated the anticancer activity of these potent antimicrobial peptides by antiproliferative assays and wound-healing assays, and the effect of peptide on the cytoskeleton alteration and cell morphology were analyzed by confocal microscopy. Results indicated that MAP-04-03 not only exhibited inhibitory effects on the proliferation (IC50=61.5 μM) and on the cell migration of MCF-7 breast cancer cells (at a concentration of 5 μM), but also affected the cytoskeleton at the concentration of 25 μM. These results demonstrated that MAP-04-03 can serve as a lead peptide analog for developing potent anticancer agents.
3. Discovery of potent antimicrobial peptide analogs of Ixosin-B
Feng-Di T Lung, Kai-Shiuan Wang, Zih-Jie Liao, Sheng-Kai Hsu, Fei-Yi Song, Chien-Chung Liou, Yu-Shan Wu Bioorg Med Chem Lett. 2012 Jun 15;22(12):4185-8. doi: 10.1016/j.bmcl.2012.04.018. Epub 2012 Apr 20.
Antimicrobial peptides (AMPs) represent the first defense line against infection when organisms are infected by pathogens. These peptides are generally good targets for the development of antimicrobial agents. Peptide amide analogs of Ixosin-B, an antimicrobial peptide with amino acid sequence of QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY, were designed, synthesized and examined for antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Within the peptides synthesized, we discovered an 11-mer peptide, KRLRRVWRRWR-amide, which exhibited potent antimicrobial activity while very little hemolytic activity in human erythrocytes was observed even at high dose level (100 μM). With further modifications, this peptide could be developed into a potent antimicrobial agent in the future.
