Rational design of antimicrobial peptides with enhanced activity and low cytotoxicity based on the structure of the arginine/histidine-rich peptide, chensinin-1.
Summary of "Rational design of antimicrobial peptides with enhanced activity and low cytotoxicity based on the structure of the arginine/histidine-rich peptide, chensinin-1."
To understand the structure-activity relationship of chensinin-1, a antimicrobial peptide with an unusual structure, and to develop novel antimicrobial peptides as therapeutic agents. METHODS AND
A series of chensinin-1 analogs were designed and synthsized by one to three replacement of glycines with leucines at the hydrophilic face of chensinin-1 or rearrangement of some of the residues in its sequence. Circular dichroism spectroscopy showed that the analogs adopted α-helical-type conformations in 50% trifluoroethanol/water but adopted β-strand-type conformations in 30 mmol l(-1) SDS. The antimicrobial activities of the peptides against Gram-positive bacteria increased 5- to 30-fold, and these increases paralleled the increases in the peptides' hydrophobicities. Their hemolytic activities also increased. Amphipathicities had little influence on the bactericidal activity of chensinin-1. All peptides caused leakage of calcein entrapped in negatively charged liposomes although with different efficiencies. The peptides did not induce leakage of calcein from uncharged liposomes.
Peptide adopted an aperiodic structure can be improved the antimicrobial potency by increasing peptide hydrophobicity. Its target is bacteria plasma membrane. SIGNIFICANCE AND IMPACT OF THE
Chensinin-1 can act as a new lead molecule for the study of AMPs with atypical structures. © 2012The Authors Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.
Faculty of Life Science, Liaoning Normal University, Dalian, 116029, People's Republic of China; Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Dalian, 116029, People's Republic of China.
This article was published in the following journal.
Name: Journal of applied microbiology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22686707
- DOI: http://dx.doi.org/10.1111/j.1365-2672.2012.05355.x
Medical and Biotech [MESH] Definitions
Structural Homology, Protein
The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN.
Antimicrobial Cationic Peptides
Small cationic peptides that are an important component, in most species, of early innate and induced defenses against invading microbes. In animals they are found on mucosal surfaces, within phagocytic granules, and on the surface of the body. They are also found in insects and plants. Among others, this group includes the DEFENSINS, protegrins, tachyplesins, and thionins. They displace DIVALENT CATIONS from phosphate groups of MEMBRANE LIPIDS leading to disruption of the membrane.
A class of antimicrobial peptides discovered in the skin of XENOPUS LAEVIS. They kill bacteria by permeabilizing cell membranes without exhibiting significant toxicity against mammalian cells.
Blood Bactericidal Activity
The natural bactericidal property of BLOOD due to normally occurring antibacterial substances such as beta lysin, leukin, etc. This activity needs to be distinguished from the bactericidal activity contained in a patient's serum as a result of antimicrobial therapy, which is measured by a SERUM BACTERICIDAL TEST.
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
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