Chemical Modification of the Carboxyl Terminal of Nisin A with Biotin does not Abolish Antimicrobial Activity Against the Indicator Organism, Kocuria rhizophila
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Nisin is an antimicrobial peptide that is widely used for food preservation. Although it has potent activity against a number of food pathogens, suggesting potential therapeutic applications, its potential for clinical use is limited by proteolytic susceptibility and poor oral bioavailability. Derivatization of nisin could overcome these issues; however, many nisin analogues, prepared by modification at the N-terminal and C-terminal have previously been shown to be inactive. A method for the C-terminal modification was developed using biotinylation as a model derivative. Purification of the modified nisin was carried out using reverse phase chromatography. Confirmation of nisin modification was confirmed by Mass Spectroscopy. The C-terminal modification of nisin resulted in only a twofold reduction in antimicrobial activity of the conjugate against the indicator organism, Kocuria rhizophila. The C-terminal modification could be used to increase the therapeutic potential of nisin by creating more favourable physicochemical characteristics. This is the first study that showed that nisin modification can be carried out successfully without destroying its antimicrobial activity.
KeywordsNisin Antimicrobial peptide Biotinylation C-terminal modification Therapeutic application
This study was supported by the Programme for Research in Third Level Institutions (PRTLI) Cycle 3 as administered by HEA, Ireland. The authors would like to thank Dr. Venkat Reddy Thangella for his assistance in the preparation of this manuscript.
- Habib W, Sakr A (1998) A colonic delivery system for the antimicrobial agent nisin. University of Leuven, College of Pharmacy, BelgiumGoogle Scholar
- Hermanson GT (1996) Bioconjugate techniques. Academic Press, London, UKGoogle Scholar
- O’Neil MJ, Smith A, Heckelman PE, Obenchain JR Jr, Gallipeau JOR, D’Arecca MA, Budavari S (eds) (2001) The Merck index: an encyclopaedia of chemicals, drugs, and biologicals. John Wiley & Sons, New York, USAGoogle Scholar
- Wiedemann I, Breukink E, van Kraaij C, Kuipers OP, Bierbaum G, de Kruijff B, Sahl HG (2001) Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity. J Biol Chem 276:1772–1779PubMedGoogle Scholar