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A theoretical approach to spot active regions in antimicrobial proteins.

ABSTRACT: BACKGROUND: Much effort goes into identifying new antimicrobial compounds able to evade the increasing resistance of microorganisms to antibiotics. One strategy relies on antimicrobial peptides, either derived from fragments released by proteolytic cleavage of proteins or designed from known antimicrobial protein regions. RESULTS: To identify these antimicrobial determinants, we developed a theoretical approach that predicts antimicrobial proteins from their amino acid sequence in addition to determining their antimicrobial regions. A bactericidal propensity index has been calculated for each amino acid, using the experimental data reported from a high-throughput screening assay as reference. Scanning profiles were performed for protein sequences and potentially active stretches were identified by the best selected threshold parameters. The method was corroborated against positive and negative datasets. This successful approach means that we can spot active sequences previously reported in the literature from experimental data for most of the antimicrobial proteins examined. CONCLUSION: The method presented can correctly identify antimicrobial proteins with an accuracy of 85% and a sensitivity of 90%. The method can also predict their key active regions, making this a tool for the design of new antimicrobial drugs.

SUBMITTER: Torrent M

PROVIDER: S-EPMC2780422 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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A theoretical approach to spot active regions in antimicrobial proteins.

Torrent Marc M Nogués Victòria M VM Boix Ester E

BMC bioinformatics 20091111

<h4>Background</h4>Much effort goes into identifying new antimicrobial compounds able to evade the increasing resistance of microorganisms to antibiotics. One strategy relies on antimicrobial peptides, either derived from fragments released by proteolytic cleavage of proteins or designed from known antimicrobial protein regions.<h4>Results</h4>To identify these antimicrobial determinants, we developed a theoretical approach that predicts antimicrobial proteins from their amino acid sequence in a ...[more]

PMID: 19906288

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Project description:A biomimetic approach to organic solvent-free microencapsulation of proteins based on the self-healing capacity of poly (DL)-lactic-co-glycolic acid (PLGA) microspheres containing glycosaminoglycan-like biopolymers (BPs), was examined. To screen BPs, aqueous solutions of BP [high molecular weight dextran sulfate (HDS), low molecular weight dextran sulfate (LDS), chondroitin sulfate (CS), heparin (HP), hyaluronic acid (HA), chitosan (CH)] and model protein lysozyme (LYZ) were combined in different molar and mass ratios, at 37 °C and pH7. The BP-PLGA microspheres (20-63 μm) were prepared by a double water-oil-water emulsion method with a range of BP content, and trehalose and MgCO3 to control microclimate pH and to create percolating pores for protein. Biomimetic active self-encapsulation (ASE) of proteins [LYZ, vascular endothelial growth factor165 (VEGF) and fibroblast growth factor (FgF-20)] was accomplished by incubating blank BP-PLGA microspheres in low concentration protein solutions at ~24 °C, for 48 h. Pore closure was induced at 42.5 °C under mild agitation for 42h. Formulation parameters of BP-PLGA microspheres and loading conditions were studied to optimize protein loading and subsequent release. LDS and HP were found to bind >95% LYZ at BP:LYZ>0.125 w/w, whereas HDS and CS bound >80% LYZ at BP:LYZ of 0.25-1 and <0.33, respectively. HA-PLGA microspheres were found to be not ideal for obtaining high protein loading (>2% w/w of LYZ). Sulfated BP-PLGA microspheres were capable of loading LYZ (~2-7% w/w), VEGF (~4% w/w), and FgF-20 (~2% w/w) with high efficiency. Protein loading was found to be dependent on the loading solution concentration, with higher protein loading obtained at higher loading solution concentration within the range investigated. Loading also increased with content of sulfated BP in microspheres. Release kinetics of proteins was evaluated in-vitro with complete release media replacement. Rate and extent of release were found to depend upon volume of release (with non-sink conditions observed <5 ml release volume for ~18 mg loaded BP-PLGA microspheres), ionic strength of release media and loading solution concentration. HDS-PLGA formulations were identified as having ideal loading and release characteristics. These optimal microspheres released ~73-80% of the encapsulated LYZ over 60 days, with >90% of protein being enzymatically active. Nearly 72% of immunoreactive VEGF was similarly released over 42 days, without significant losses in heparin binding affinity in the release medium.

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A theoretical approach to spot active regions in antimicrobial proteins.

Publications

A theoretical approach to spot active regions in antimicrobial proteins.

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