title: Protegrin structure-activity relationships: using homology models of synthetic sequences to determine structural characteristics important for activity.
abstract: The protegrin family of antimicrobial peptides is among the shortest in sequence length while remaining very active against a variety of microorganisms. The major goal of this study is to characterize easily calculated molecular properties, which quantitatively show high correlation with antibacterial activity. The peptides studied have high sequence similarity but vary in activity over more than an order of magnitude. Hence, sequence analysis alone cannot be used to predict activity for these peptides. We calculate structural properties of 62 protegrin and protegrin-analogue peptides and correlate them to experimental activities against six microbe species, as well as hemolytic and cytotoxic activities. Natural protegrins structures were compared with synthetic derivatives using homology modeling, and property descriptors were calculated to determine the characteristics that confer their antimicrobial activity. A structure-activity relationship study of all these peptides provides information about the structural properties that affect activity against different microbial species.
authors.affiliation: Department of Chemical Engineering and Materials Science, and Digital Technology Center, University of Minnesota, 421 Washington Ave SE, Minneapolis, MN 55455, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ostberg
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Kaznessis
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002584:Cervix Uteri / Q000166:cytology; D004848:Epithelium / Q000187:drug effects*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides