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.

Multifunctional Nano‐Biointerfaces: Cytocompatible Antimicrobial Nanocarriers from Stabilizer‐Free Cubosomes

“…The only AMP from the cathelicidin family found in the human body is LL‐37 . Possessing antimicrobial effects while enhancing cell migration and proliferation makes AMPs such as LL‐37 a desirable therapeutic agent for medical applications such as wound‐healing . However, the inherent complex properties of AMPs, including their low solubility in water, and their low stability in the biological environment result in low bioavailability and have hindered their broader therapeutic application …”

Cationic antimicrobial peptides and periodontal physiopathology: A systematic review

“…Azurocidin exhibits a large range of biological functions such as modulation of inflammatory process, chemotaxis toward monocytes and antimicrobial properties …”

“…Azurocidin exhibits a large range of biological functions such as modulation of inflammatory process, chemotaxis toward monocytes and antimicrobial properties. [75][76][77][78][79] Azurocidin level in GCF was higher in periodontal inflamed sites than in healthy ones. 80 Azurocidin is part of the twenty-five proteins or peptides detected to be higher in GCF of periodontitis patients than in healthy ones.…”

Antimicrobial Peptides Derived from the Immune Defense Protein CAP37 Inhibit TLR4 Activation by S100A9

“…CAP37-derived peptides, spanning residues 20 to 44, 95 to 122, and 120 to 146 of the protein, were synthesized by CSBio (Menlo Park, CA, USA) with a purity of ≥95%, as previously described. 13 Peptide analogs 120 to 146 WH used in this study were modified from the native sequence of CAP37 (120-146 QR). The native residues Q and R in positions 131 and 132 were substituted by W and H, respectively.…”

“…Corneal abrasion was performed as described before. 13 Briefly, mice (8-week-old female C57BL/6) were anesthetized using ketamine (100 mg/kg) and xylazine (10 ng/kg); to minimize suffering, the systemic analgesic buprenorphine sustained release (ZooPharm, Inc., Laramie, WY, USA) was administered subcutaneously (1 mg/kg) before corneal abrasion was performed. A 2-mm trephine (Integra Miltex, York, PA, USA) was first used to demarcate the cornea of the right eye of the mouse.…”