Poly(2-oxazoline)–Antibiotic Conjugates with Penicillins

Abstract

The conjugation of antibiotics with polymers is rarely done, but it might be a promising alternative to low-molecular-weight derivatization. The two penicillins penicillin G (PenG) and penicillin V (PenV) were attached to the end groups of different water-soluble poly(2-oxazoline)s (POx) via their carboxylic acid function. This ester group was shown to be more stable against hydrolysis than the β-lactam ring of the penicillins. The conjugates are still antimicrobially active and up to 20 times more stable against penicillinase catalyzed hydrolysis. The antibiotic activity of the conjugates against Staphylococcus aureus in the presence of penicillinase is up to 350 times higher compared with the free antibiotics. Conjugates with a second antimicrobial function, a dodecyltrimethylammonium group (DDA-X), at the starting end of the PenG and PenV POx conjugates are more antimicrobially active than the conjugates without DDA-X and show high activity in the presence of penicillinase. For example, the conjugates DDA-X-PEtOx-PenG and DDA-X-PEtOx-PenV are 200 to 350 times more active against S. aureus in the presence of penicillinase and almost as effective as the penicillinase stable cloxacollin (Clox) under these conditions. These conjugates show even greater activity compared to cloxacollin without this enzyme present. Further, both conjugates kill Escherichia coli more effectively than PenG and Clox.

Straightforward access to biocompatible poly(2-oxazoline)-coated nanomaterials by polymerization-induced self-assembly

“…5 Several studies have focused on the synthesis of functional PAOx to achieve functional hydrogels, [6][7][8] surface coatings, 9 and polymer-peptide/protein/drug conjugates. 10,11 Besides, the interest in PAOx-based complex structures is also increasing. 12 PEtOx brush-arm star and comb-shaped polymers incorporating nitroxide radicals and perfluorinated segments, respectively, have been reported for magnetic resonance imaging.…”

Entropically driven Polymeric Enzyme Inhibitors by End‐Group directed Conjugation

“…[9] Furthermore,t he bacterial topoisomerase II and IV inhibitor ciprofloxacina nd thet ranspeptidase inhibitor penicillin were attached to poly(2-oxazolines).T his changed the activityp rofiles of the antibioticsa nd increased the hydrolysis stability against penicillinased egradation in cases of the penicillin conjugates. [10,11] One example for the third class are chitinase inhibitors that are oligo-or polysaccharides with specific binding to the active site of the enzyme. [12] Polyacrylica cid derivatives inhibitt he activity of luminale nzymes, for example, trypsin and carboxypeptidase.…”

Full Thermal Switching of Enzymes by Thermoresponsive Poly(2‐oxazoline)‐Based Enzyme Inhibitors

“…The process is fully reversible and does not interfere with the protein'sa ctivity.T his complete switching can be used to fully thermally control the bioactivity of these widely used, important enzymes. Biocompatible poly(2-oxazoline)s,w hich have been shown to be suitable for the conjugationo fv arious drugs and proteins, [28,29] have already been successfully used to conjugate inhibitors for collagenases, [30] d-alanine transpeptidase, [31] and gyrase, [32,33] whicha re highly relevant for biomedical applications. Therefore, the approach presented herew ill likely be applicable to abroad range of temperature-controllable enzymatic processes.T he selectivity of some of the inhibitors shown here might be used to temperature control the activity of enzymes in multienzyme systems.…”