| Autor: |
Slootweg JC; Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University , P.O. Box 80082, 3508 TB Utrecht, The Netherlands., van der Wal S, Quarles van Ufford HC, Breukink E, Liskamp RM, Rijkers DT |
| Jazyk: |
angličtina |
| Zdroj: |
Bioconjugate chemistry [Bioconjug Chem] 2013 Dec 18; Vol. 24 (12), pp. 2058-66. Date of Electronic Publication: 2013 Dec 05. |
| DOI: |
10.1021/bc400401k |
| Abstrakt: |
Functionalization of the lantibiotic nisin with fluorescent reporter molecules is highly important for the understanding of its mode of action as a potent antimicrobial peptide. In addition to this, multimerization of nisin to obtain multivalent peptide constructs and conjugation of nisin to bioactive molecules or grafting it on surfaces can be attractive methods for interference with bacterial growth. Here, we report a convenient method for the synthesis of such nisin conjugates and show that these nisin derivatives retain both their antimicrobial activity and their membrane permeabilizing properties. The synthesis is based on the Cu(I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC) as a bioorthogonal ligation method for large and unprotected peptides in which nisin was C-terminally modified with propargylamine and subsequently efficiently conjugated to a series of functionalized azides. Two fluorescently labeled nisin conjugates together with a dimeric nisin construct were prepared while membrane insertion as well as antimicrobial activity were unaffected by these modifications. This study shows that C-terminal modification of nisin does not deteriorate biological activity in sharp contrast to N-terminal modification and therefore C-terminally modified nisin analogues are valuable tools to study the antibacterial mode of action of nisin. Furthermore, the ability to use stoichiometric amounts of the azide containing molecule opens up possibilities for surface tethering and more complex multivalent structures. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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