Protegrin 1
Porcine antimicrobial peptide with beta-hairpin structure that rapidly kills multidrug-resistant bacteria through membrane disruption.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C84H134N26O17S4 |
| Molecular Weight | 1943 Da |
| Peptide Class | Porcine Antimicrobial Peptide (18 aa) |
| Sequence | RGGRLCYCRRRFCVCVGR-NH2 |
| Disulfide Bonds | 2 (Cys4-Cys15, Cys6-Cys13) |
| Origin | Porcine leukocytes |
Structure
Protegrin 1 is an 18-amino acid beta-hairpin antimicrobial peptide from porcine leukocytes. Two disulfide bonds stabilize a rigid antiparallel beta-hairpin structure with cationic residues on one face and hydrophobic residues on the other. The compact structure provides stability against proteolytic degradation.
Mechanism of Action
Protegrin 1 inserts into bacterial membranes as oligomeric beta-barrel pores, causing rapid membrane depolarization and cell lysis. The rigid beta-hairpin structure allows efficient membrane insertion, and the cationic residues provide selectivity for anionic bacterial membranes over zwitterionic mammalian membranes.
Clinical Applications
- MDR infections: Active against MRSA, VRE, and resistant gram-negatives
- Lead compound: Iseganan (synthetic analog) developed for clinical use
- Oral mucositis: Iseganan oral rinse (Phase III)
- Ventilator-associated pneumonia: Iseganan nebulized (Phase III)
Pharmacology
- Spectrum: Broadest spectrum AMP (gram-positive, gram-negative, fungi, enveloped viruses)
- Potency: Rapid killing (minutes)
- Salt resistance: Maintains activity in physiological salt
- Stability: Resistant to proteolysis due to disulfide bonds
References
- Kokryakov, V.N., et al. (1993). Protegrins: leukocyte antimicrobial peptides. Journal of Cell Science, 104, 1053-1063.
- Steinberg, D.A., et al. (1997). Protegrin-1: a potent antimicrobial peptide. Antimicrobial Agents and Chemotherapy, 41, 1738-1742.
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