Abstract
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.
Original language | English |
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Pages (from-to) | 2058-2066 |
Number of pages | 9 |
Journal | Bioconjugate Chemistry |
Volume | 24 |
Issue number | 12 |
DOIs | |
Publication status | Published - 18 Dec 2013 |