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Antimicrobial Agents and Chemotherapy, June 2005, p. 2412-2420, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2412-2420.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effects of Acyl versus Aminoacyl Conjugation on the Properties of Antimicrobial Peptides

Inna S. Radzishevsky, Shahar Rotem, Fadia Zaknoon, Leonid Gaidukov, Arie Dagan, and Amram Mor*

Department of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel

Received 29 September 2004/ Returned for modification 5 December 2004/ Accepted 23 January 2005

To investigate the importance of increased hydrophobicity at the amino end of antimicrobial peptides, a dermaseptin derivative was used as a template for a systematic acylation study. Through a gradual increase of the acyl moiety chain length, hydrophobicity was monitored and further modulated by acyl conversion to aminoacyl. The chain lengths of the acyl derivatives correlated with a gradual increase in the peptide's global hydrophobicity and stabilization of its helical structure. The effect on cytolytic properties, however, fluctuated for different cells. Whereas acylation gradually enhanced hemolysis of human red blood cells and antiprotozoan activity against Leishmania major, bacteria displayed a more complex behavior. The gram-positive organism Staphylococcus aureus was most sensitive to intermediate acyl chains, while longer acyls gradually led to a total loss of activity. All acyl derivatives were detrimental to activity against Escherichia coli, namely, but not solely, because of peptide aggregation. Although aminoacyl derivatives behaved essentially similarly to the nonaminated acyls, they displayed reduced hydrophobicity, and consequently, the long-chain acyls enhanced activity against all microorganisms (e.g., by up to 12-fold for the aminolauryl derivative) but were significantly less hemolytic than their acyl counterparts. Acylation also enhanced bactericidal kinetics and peptide resistance to plasma proteases. The similarities and differences upon acylation of MSI-78 and LL37 are presented and discussed. Overall, the data suggest an approach that can be used to enhance the potencies of acylated short antimicrobial peptides by preventing hydrophobic interactions that lead to self-assembly in solution and, thus, to inefficacy against cell wall-containing target cells.

* Corresponding author. Mailing address: Laboratory of Antimicrobial Investigation, Department of Biotechnology & Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel. Phone: (972) 4-829-3340. Fax: (972) 4-829-3399. E-mail: amor{at}tx.technion.ac.il.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2412-2420, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2412-2420.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sarig, H., Rotem, S., Ziserman, L., Danino, D., Mor, A. (2008). Impact of Self-Assembly Properties on Antibacterial Activity of Short Acyl-Lysine Oligomers. Antimicrob. Agents Chemother. 52: 4308-4314 [Abstract] [Full Text]  
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