title: Evaluation of the Therapeutic Properties of Mastoparan- and Sifuvirtide- Derivative Antimicrobial Peptides Using Chemical Structure-Function Relationship - in vivo and in silico Approaches.
abstract: Antimicrobial peptides, also called body defense peptides, are chemical structures widely distributed across the animal and vegetal kingdoms that have a fundamental role as part of the immune system. These peptides are used against a wide range of pathogens, such as Gram-negative and - positive bacteria, fungi and viruses, etc. Their action spectrum makes them important for the pharmaceutical industry, as they could represent templates for the design of new and more potent structures by using drug design and drug delivery systems. Here we present the antimicrobial activity against Bacillus subtilis (expressed as minimal inhibitory concentration values) for 33 mastoparan analogs and their new derivatives by quantitative structure-activity relationship method (2D, aligned and also non-aligned 3D-QSAR). We establish the contribution to antimicrobial activity of molecular descriptors like hydrophobicity, hydrogen bond donor and steric hindrance, correlated with contributions from the membrane environment (sodium, potassium, chloride ions). Also the studies of HIV-1 fusion inhibitor sifuvirtide and its analogs are presented in context of interaction with lipid structures during fusion and delivery of these drugs.
authors.forename: Speranta
authors.initials: S
authors.lastname: Avram
authors.affiliation: Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 91-95th Independentei Str., Bucharest-050095. maria.mernea@bio.unibuc.ro.
authors.forename: Maria
authors.initials: M
authors.lastname: Mernea
authors.forename: Florin
authors.initials: F
authors.lastname: Borcan
authors.forename: Dan
authors.initials: D
authors.lastname: Mihailescu
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D010455:Peptides / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014862:Wasp Venoms / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D036341:Intercellular Signaling Peptides and Proteins; D008055:Lipids; D010455:Peptides; D014862:Wasp Venoms; C505768:sifuvirtide; C037500:mastoparan