RESUMO
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.
Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Antineoplásicos/química , Proteínas de Artrópodes/química , Amidas/química , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/toxicidade , Antineoplásicos/toxicidade , Proteínas de Artrópodes/toxicidade , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Humanos , Células MCF-7 , Estrutura Secundária de ProteínaRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Proteínas de Artrópodes/farmacologia , Eritrócitos/parasitologia , Escherichia coli/efeitos dos fármacos , Oligopeptídeos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/química , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/química , Proteínas de Artrópodes/síntese química , Proteínas de Artrópodes/química , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Oligopeptídeos/síntese química , Oligopeptídeos/química , Relação Estrutura-AtividadeRESUMO
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.