TY  - JOUR
A1  - Borova, Solomiia
A1  - Schlutt, Christine
A1  - Nickel, Joachim
A1  - Luxenhofer, Robert
T1  - A Transient Initiator for Polypeptoids Postpolymerization α‐Functionalization via Activation of a Thioester Group
JF  - Macromolecular Chemistry and Physics
N2  - Here, a postpolymerization modification method for an α-terminal functionalized poly-(N-methyl-glycine), also known as polysarcosine, is introduced. 4-(Methylthio)phenyl piperidine-4-carboxylate as an initiator for the ring-opening polymerization of N-methyl-glycine-N-carboxyanhydride followed by oxidation of the thioester group to yield an α-terminal reactive 4-(methylsulfonyl)phenyl piperidine-4-carboxylate polymer is utilized. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes, and model proteins. The new initiator yielded polymers with well-defined molar mass, low dispersity, and high end-group fidelity, as observed by gel permeation chromatography, nuclear magnetic resonance spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. The introduced method can be of great interest for bioconjugation, but requires optimization, especially for protein conjugation.
KW  - ring-opening polymerization
KW  - bioconjugation
KW  - functional initiators
KW  - polypeptoids
KW  - postpolymerization modification
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-257587
VL  - 223
IS  - 3
ER  - 
TY  - JOUR
A1  - Siverino, Claudia
A1  - Fahmy-Garcia, Shorouk
A1  - Mumcuoglu, Didem
A1  - Oberwinkler, Heike
A1  - Muehlemann, Markus
A1  - Mueller, Thomas
A1  - Farrell, Eric
A1  - van Osch, Gerjo J. V. M.
A1  - Nickel, Joachim
T1  - Site-directed immobilization of an engineered bone morphogenetic protein 2 (BMP2) variant to collagen-based microspheres induces bone formation in vivo
JF  - International Journal of Molecular Sciences
N2  - For the treatment of large bone defects, the commonly used technique of autologous bone grafting presents several drawbacks and limitations. With the discovery of the bone-inducing capabilities of bone morphogenetic protein 2 (BMP2), several delivery techniques were developed and translated to clinical applications. Implantation of scaffolds containing adsorbed BMP2 showed promising results. However, off-label use of this protein-scaffold combination caused severe complications due to an uncontrolled release of the growth factor, which has to be applied in supraphysiological doses in order to induce bone formation. Here, we propose an alternative strategy that focuses on the covalent immobilization of an engineered BMP2 variant to biocompatible scaffolds. The new BMP2 variant harbors an artificial amino acid with a specific functional group, allowing a site-directed covalent scaffold functionalization. The introduced artificial amino acid does not alter BMP2′s bioactivity in vitro. When applied in vivo, the covalently coupled BMP2 variant induces the formation of bone tissue characterized by a structurally different morphology compared to that induced by the same scaffold containing ab-/adsorbed wild-type BMP2. Our results clearly show that this innovative technique comprises translational potential for the development of novel osteoinductive materials, improving safety for patients and reducing costs.
KW  - bone morphogenetic protein 2 (BMP2)
KW  - bone regeneration
KW  - covalent coupling
KW  - subcutaneous animal model
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284572
SN  - 1422-0067
VL  - 23
IS  - 7
ER  -