HPRP-A1, a 15-mer α-helical cationic peptide, was derived from N-terminus of ribosomal protein L1 (RpL1) of Helicobacter pylori. In this study, HPRP-A1 was used as a framework to obtain a series of peptide analogs wi...HPRP-A1, a 15-mer α-helical cationic peptide, was derived from N-terminus of ribosomal protein L1 (RpL1) of Helicobacter pylori. In this study, HPRP-A1 was used as a framework to obtain a series of peptide analogs with different hydrophobicity by single amino acid substitutions in the center of nonpolar face of the amphipathic helix in order to systematically study the effect of hydrophobicity on biological activities of -helical antimicrobial peptides. Hydrophobicity and net charge of peptides played key roles in the biological activities of these peptide analogs; HPRP-A1 and peptide analogs with relative higher hydrophobicity exerted broad spectrum antimicrobial activity against Gram-negative bacteria, Gram-positive bacteria and pathogenic fungi, but also showed stronger hemolytic activity; the change of hydrophobicity and net charge of peptides had similar effects with close trend and extent on antibacterial activities and antifungal activities. This indicated that there were certain correlations between the antibacterial mode of action and the antifungal mode of action of these peptides in this study. The peptides exhibited antimicrobial specificity for bacteria and fungi, which provided potentials to develop new antimicrobial drugs for clinical practices.展开更多
Using two series of de novo designed antimicrobial peptides,we studied the effects of peptide length and hydrophobicity/charge(H/C) ratio on the antimicrobial activities.For these peptides,a correlation was establishe...Using two series of de novo designed antimicrobial peptides,we studied the effects of peptide length and hydrophobicity/charge(H/C) ratio on the antimicrobial activities.For these peptides,a correlation was established between their antimicrobial efficacy and the leakage,aggregation,and fusion activities on artificial membrane.The results showed that peptides with an H/C ratio of 1.3,and a length of about half of the membrane thickness caused most potent membrane leakage,and negligible membrane aggregation and fusion.In addition,such peptide also exhibited the highest antimicrobial activity.Analysis of the hydrophobic and electrostatic interactions showed that the strength,the order and the position of these interactions determined the activities of the peptides on the artificial membrane and thus the antimicrobial efficacy.Further analyses on the tilt angle of the peptides on the membrane surface indicated that the peptides distorted the membrane in a dynamic mode,instead of being fixed in the membrane at a constant angle.展开更多
基金Natural Science Foundation of Jilin Province(201015130)the Youth Foundation of Jilin Province (20100126)
文摘HPRP-A1, a 15-mer α-helical cationic peptide, was derived from N-terminus of ribosomal protein L1 (RpL1) of Helicobacter pylori. In this study, HPRP-A1 was used as a framework to obtain a series of peptide analogs with different hydrophobicity by single amino acid substitutions in the center of nonpolar face of the amphipathic helix in order to systematically study the effect of hydrophobicity on biological activities of -helical antimicrobial peptides. Hydrophobicity and net charge of peptides played key roles in the biological activities of these peptide analogs; HPRP-A1 and peptide analogs with relative higher hydrophobicity exerted broad spectrum antimicrobial activity against Gram-negative bacteria, Gram-positive bacteria and pathogenic fungi, but also showed stronger hemolytic activity; the change of hydrophobicity and net charge of peptides had similar effects with close trend and extent on antibacterial activities and antifungal activities. This indicated that there were certain correlations between the antibacterial mode of action and the antifungal mode of action of these peptides in this study. The peptides exhibited antimicrobial specificity for bacteria and fungi, which provided potentials to develop new antimicrobial drugs for clinical practices.
基金supported by the National Natural Science Foundation of China(21574002,21174007)the Beijing Natural Science Foundation(5132015)the Nantong Jianghai Talent Program
文摘Using two series of de novo designed antimicrobial peptides,we studied the effects of peptide length and hydrophobicity/charge(H/C) ratio on the antimicrobial activities.For these peptides,a correlation was established between their antimicrobial efficacy and the leakage,aggregation,and fusion activities on artificial membrane.The results showed that peptides with an H/C ratio of 1.3,and a length of about half of the membrane thickness caused most potent membrane leakage,and negligible membrane aggregation and fusion.In addition,such peptide also exhibited the highest antimicrobial activity.Analysis of the hydrophobic and electrostatic interactions showed that the strength,the order and the position of these interactions determined the activities of the peptides on the artificial membrane and thus the antimicrobial efficacy.Further analyses on the tilt angle of the peptides on the membrane surface indicated that the peptides distorted the membrane in a dynamic mode,instead of being fixed in the membrane at a constant angle.
