Stichting Katholieke Universiteit, Meer in Het Bijzonder Radboud Universiteit Nijmegen

Stichting Katholieke Universiteit

Stichting Radboud Universiteit

Stichting Katholieke Universiteit / Radboud University Nijmegen Medical Centre

Alan Edward Rowan

Erik Schwartz

Paul Kouwer

Matthieu Koepf

Heather Joy Kitto

Jeroen Johannes Lambertus Maria Cornelissen

Roeland Johannes Maria Nolte

Carl Gustav Figdor

Daniël Schoenmakers

Paula De Almeida

Maarten Jaspers

Egbert Oosterwijk

Wouter F J Feitz

Petrus Johannes Geutjes

Christopher Wilson

Zaskia Hillet Eksteen Akeroyd

Wouter Fj Feitz

A double network hydrogel including a polymer (A) having a persistence length between 10 and 1000 nm; a flexible polymer (B), wherein the persistence length is measured according to single molecule force microscopy measurement, wherein polymer (B) has an extended coil conformation at a first condition and a collapsed globular conformation at a second condition. Polymer (A) preferably is a polyisocyanate, while polymer (B) is a crosslinked flexible polymer like for example PNIPAM. A method for making a double network hydrogel.

Biomimetic double network hydrogels

A polymer hydrogel having a polymer formed by the crosslinking reaction of a polymeric unit A according to formula (I), with a crosslinking unit B according to formula (II) and water, wherein n=100-10,000, preferable 250-2500, more preferable 500-1500; m=independently 2-10, preferably 3 or 4; FG is a functional moiety that can be covalently coupled to the complementary functional moiety F1 or F2 of the crosslinking unit (B); k=0.01-0.05; h=0, 1 or 2; the spacer is an organic moiety, having a main chain comprising at least two functional moieties F1 and F2, wherein the length of the crosslinker in the extended conformation as determined by molecular modeling (including spacer and functional groups F1 and F2) is between 2.5 and 12 nm, or wherein the length is between 20 and 80 atoms.

Biomimetic networks comprising polyisocyanopeptide hydrogels

The present invention relates to protein constructs that comprise one or more peptides, proteins, factors, compounds or other components as further described herein that are linked to and/or are linked to each other via a helical polymeric backbone. The constructs of the invention are suitable for administration to a human or animal body and can be used for pharmaceutical purposes, for example, for immunotherapy, such as for treating cancer and for other immunological applications, as well as for other therapeutic, prophylactic and/or diagnostic purposes.

Immunomodulatory protein constructs with a helical polymeric backbone

A process for making an oligo(alkylene glycol) functionalized co-polyisocyanopeptide, wherein the process includes the steps of: i) copolymerizing a first comonomer of an oligo(alkylene glycol) functionalized isocyanopeptide grafted with a linking group and a second comonomer of a non-grafted oligo(alkylene glycol) functionalized isocyanopeptide, wherein the molar ratio between the first comonomer and the second comonomer is 1:500 and 1:30 and ii) adding a reactant of a spacer unit and a cell adhesion factor to the copolymer obtained by step i), wherein the spacer unit is represented by general formula A-L-B, wherein the linking group and group A are chosen to react and form a first coupling and the cell adhesion factor and group B are chosen to react and form a second coupling, wherein the first coupling and the second coupling are independently selected from the group consisting of alkyne-azide coupling, dibenzocyclooctyne-azide coupling, oxanorbornmadiene-based-azide couplings, vinylsulphone-thiol coupling, maleimide-thiol coupling, methyl methacrylate-thiol coupling, ether coupling, thioether coupling, biotin-strepavidin coupling, amine-carboxylic acid resulting in amides linkages, alcohol-carboxylic acid coupling resulting in esters linkages and NHS-Ester (N-Hydroxysuccinimide ester)-amine coupling and wherein group L is a linear chain segment having 10-60 bonds between atoms selected from C, N, O and S in the main chain.

Polymer suitable for use in cell culture

The present invention relates to a process for the preparation of oligo(alkylene glycol)-functionalized polyisocyanopeptides comprising the steps of functionalizing an isocyanopeptide with oligo-(alkylene glycol) side chains and subsequently polymerizing the oligo-alkylene glycol-functionalized isocyanopeptides. Several isocyanopeptides may be functionalized with various linear or non-linear oligo-(alkylene glycol) side chains having variable chain length. The alkylene glycol may be selected from the group consisting of ethylene-, propylene-, butylene- or pentylene glycol. Preferably, the isocyanopeptides are functionalized with at least three ethylene glycol side chains. The peptides may comprise L-amino acids, D-amino acids or D, L-amino acids. The obtained oligoalkylene-functionalized polyisocyanopeptides are a new class of materials with unique thermo-responsive properties.

Method for the preparation of high molecular weight oligo(alkylene glycol) functionalized polyisocyanopeptides

The present invention relates to a process for the preparation of oligo(alkylene glycol) functionalized polyisocyanopeptides comprising the steps of functionalizing an isocyanopeptide with oligo-(alkylene glycol) side chains and subsequently polymerizing the oligo-alkylene glycol functionalized isocyanopeptides. Several isocyanopeptide may be functionalized with various linear or non-linear oligo-(alkylene glycol) side chains having variable chain length. The alkylene glycol may be selected from the group consisting of ethylene-, propylene-, butylene- or pentylene glycol. Preferably the isocyanopeptides are functionalized with at least 3 ethylene glycol side chains. The peptides may comprise L aminoacids, D-aminoacids or D, L-aminoacids. The obtained oligoalkylene functionalized polyisocyanopeptides are a new class of materials with unique thermo-responsive properties.

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Nijmegen, Netherlands

Alan Edward Rowan