Short KR-12 analogs designed from human cathelicidin LL-37 possessing both antimicrobial and antiendotoxic activities without mammalian cell toxicity.
Jacob. Binu B; Park. Il-Seon IS; Bang. Jeong-Kyu JK; Shin. Song Yub SY
Key Findings
- KR-12 analogs a2‑a5 keep strong antimicrobial power against MRSA at low micromolar levels
- Analogs a2‑a4 show high selectivity for bacteria over red blood cells, indicating low mammalian toxicity
- Anti‑endotoxin (LPS‑neutralizing) activity depends on a balance of hydrophobicity and positive charge; a5 is the most potent but not less toxic than the original peptide
Practical Outcomes
- These results suggest that short, engineered LL-37 fragments could become safe, effective antimicrobial or anti‑inflammatory agents in the future, but more animal and human testing is needed before anyone can consider using them as supplements or therapies.
Summary
Scientists tweaked a tiny piece of the human immune peptide LL-37 to make new versions that can kill tough bacteria like MRSA and calm down harmful inflammation without hurting human cells in lab tests. While promising, these findings are still early‑stage and not ready for personal use.
Abstract
KR-12 (residues 18-29 of LL-37) was known to be the smallest peptide of human cathelicidin LL-37 possessing antimicrobial activity. In order to optimize α-helical short antimicrobial peptides having both antimicrobial and antiendotoxic activities without mammalian cell toxicity, we designed and synthesized a series of KR-12 analogs. Highest hydrophobic analogs KR-12-a5 and KR-12-a6 displayed greater inhibition of lipopolysaccharide (LPS)-stimulated tumor necrosis factor-α production and higher LPS-binding activity. We have observed that antimicrobial activity is independent of charge, but LPS neutralization requires a balance of hydrophobicity and net positive charge. Among KR-12 analogs, KR-12-a2, KR-12-a3 and KR-12-a4 showed much higher cell specificity for bacteria over erythrocytes and retained antiendotoxic activity, relative to parental LL-37. KR-12-a5 displayed the strongest antiendotoxic activity but almost similar cell specificity as compared with LL-37. Also, these KR-12 analogs (KR-12-a2, KR-12-a3, KR-12-a4 and KR-12-a5) exhibited potent antimicrobial activity (minimal inhibitory concentration: 4 μM) against methicillin-resistant Staphylococcus aureus. Taken together, these KR-12 analogs have the potential for future development as a novel class of antimicrobial and anti-inflammatory therapeutic agents.
Study Information
pubmed
2013
2013-09-17T00:00:00.000Z
10.1002/psc.2552
96
39