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Entropically driven Polymeric Enzyme Inhibitors by End‐Group directed Conjugation
Author(s) -
Hijazi Montasser,
Krumm Christian,
Cinar Suelyman,
Arns Loana,
Alachraf Wasim,
Hiller Wolf,
Schrader Wolfgang,
Winter Roland,
Tiller Joerg C.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800168
Subject(s) - isothermal titration calorimetry , chemistry , dissociation constant , horseradish peroxidase , polymer , enzyme , polymer chemistry , titration , stereochemistry , combinatorial chemistry , organic chemistry , biochemistry , receptor
A new generic concept for polymeric enzyme inhibitors is presented using the example of poly(2‐methyl‐2‐oxazoline) (PMOx) terminated with an iminodiacetate (IDA) function. These polymers are shown to be non‐competitive inhibitors for horseradish peroxidase (HRP). Mechanistic investigations revealed that the polymer is directed to the protein by its end group and collapses at the surface in an entropy‐driven process as shown by isothermal titration calorimetry. The dissociation constant of the complex was determined as the inhibition constant K i using HRP kinetic activity measurements. Additional experiments suggest that the polymer does not form a diffusion layer around the protein, but might inhibit by inducing minor conformational changes in the protein. This kind of inhibitor offers new avenues towards designing bioactive compounds.