title: A multifunctional peptide based on the neutrophil immune defense molecule, CAP37, has antibacterial and wound-healing properties.
abstract: CAP37, a protein constitutively expressed in human neutrophils and induced in response to infection in corneal epithelial cells, plays a significant role in host defense against infection. Initially identified through its potent bactericidal activity for Gram-negative bacteria, it is now known that CAP37 regulates numerous host cell functions, including corneal epithelial cell chemotaxis. Our long-term goal is to delineate the domains of CAP37 that define these functions and synthesize bioactive peptides for therapeutic use. We report the novel finding of a multifunctional domain between aa 120 and 146. Peptide analogs 120-146 QR, 120-146 QH, 120-146 WR, and 120-146 WH were synthesized and screened for induction of corneal epithelial cell migration by use of the modified Boyden chamber assay, antibacterial activity, and LPS-binding activity. In vivo activity was demonstrated by use of mouse models of sterile and infected corneal wounds. The identity of the amino acid at position 132 (H vs. R) was important for cell migration and in vivo corneal wound healing. All analogs demonstrated antimicrobial activity. However, analogs containing a W at position 131 showed significantly greater antibacterial activity against the Gram-negative pathogen Pseudomonas aeruginosa. All analogs bound P. aeruginosa LPS. Topical administration of analog 120-146 WH, in addition to accelerating corneal wound healing, effectively cleared a corneal infection as a result of P. aeruginosa. In conclusion, we have identified a multifunctional bioactive peptide, based on CAP37, that induces cell migration, possesses antibacterial and LPS-binding activity, and is effective at healing infected and noninfected corneal wounds in vivo.
authors.affiliation: Departments of *Pharmaceutical Sciences, Pathology, and Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Kasus-Jacobi
authors.affiliation: Departments of *Pharmaceutical Sciences, Pathology, and Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Noor-Mohammadi
authors.affiliation: Departments of *Pharmaceutical Sciences, Pathology, and Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Gina L
authors.initials: GL
authors.lastname: Griffith
authors.affiliation: Departments of *Pharmaceutical Sciences, Pathology, and Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Hinsley
authors.affiliation: Departments of *Pharmaceutical Sciences, Pathology, and Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Mathias
authors.affiliation: Departments of *Pharmaceutical Sciences, Pathology, and Cell Biology and Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA anne-pereira@ouhsc.edu.
authors.forename: H Anne
authors.initials: HA
authors.lastname: Pereira
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001798:Blood Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D065306:Corneal Injuries / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
chemical_list: C062991:AZU1 protein, human; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins
keywords: Pseudomonas; antimicrobial peptide; cell migration; corneal wound healing; keratitis