Aston University

Martin Griffin

Daniel Lee Rathbone

Zhuo Wang

Paul Christian

Brian Gibbons

Deborah J Heath

Kamila Pytel

Richard Jones

Leonas Eduard Badarau

Ian G Coutts

Russell Collighan

Robert E Saint

Daniel Rathbone

Elisabetta Verderio Edwards

David Chau

The present invention relates to novel compounds of Formula I capable of inhibiting tissue transglutaminase, and uses of the same in medicine. In particular, the invention provides compounds for use in the treatment of prevention of disease and conditions such as fibrosis (e.g. cystic fibrosis), scarring, neurodegenerative diseases (e.g. Alzheimer's disease, Huntington's disease and Parkinson's disease), autoimmune diseases (e.g. multiple sclerosis and coeliac disease), thrombosis, proliferative disorders (e.g. cancers), AIDS, psoriasis and inflammation (e.g. chronic inflammatory diseases).

Acylpiperazines as inhibitors of transglutaminase and their use in medicine

The present invention provides a polypeptides capable of modulating tissue transglutaminase-induced cell behavior wherein the polypeptide comprises or consists of either (a) the amino acid sequence of a heparin-binding site of a tissue transglutaminase, or a functional fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant or derivative thereof or (b) an antibody capable of binding to a heparin-binding site of a tissue transglutaminase, or an antigen-binding fragment or derivative thereof. In one embodiment, the heparin-binding site of a tissue transglutaminase comprises or consists of an amino acid sequence of SEQ ID NO: 1, The invention further provides medical uses of the polypeptides of the invention and methods of treatment using the same.

Polypeptides and use thereof

Novel Amino Acid Derivatives and Pharmaceutical Uses Thereof Provided are novel compounds of Formula I: 

Amino acid derivatives and pharmaceutical uses thereof

The present invention provides a medical implant material comprising mammalian transglutaminase and a polymer, wherein the transglutaminase is provided in the absence of free divalent metal ions and wherein the polymer is associated with the transglutaminase binding protein. Preferably, the transglutaminase is a tissue transglutaminase, which is coated on, impregnated into or covalently linked to the polymer. The polymer may be naturally occuring or synthetic, and may be biodegradable or non-biodegradable. The medical implant material may further comprise a reinforcing agent and/or one or more additional polymers. The invention further provides the use of a mammalian transglutaminase in a method for improving the biocompatibility of a medical implant material, the method comprising the steps of (i) providing a medical implant material comprising a polymer associated with a binding protein for binding the transglutaminase, and (ii) treating said material with a mammalian transglutaminase.

Medical implant materials containing immobilized transglutaminase

The present invention relates to use of a transglutaminase in the preparation of a medicament for inhibiting angiogenesis. Preferably, the transglutaminase is a human tissue transglutaminase. Advantageously, the medicament is for treating cancer, rheumatoid arthritis, retinopathy and/or psoriasis. Additionally, the invention relates to compositions comprising a transglutaminase in an amount sufficient to inhibit angiogenesis.

Transglutaminase for inhibiting angiogenesis

A method for diagnosing coeliac disease in a patient comprising (a) providing an antibody sample from the patient to be tested, (b) contacting said antibody sample with cross-linked extracellular matrix (ECM) material immobilized on a surface and (c) detecting binding of antibodies present in the sample to the ECM-coated surface, wherein the binding of antibodies present in the sample to the ECM-coated surface being indicative of a positive diagnosis. Preferably, step (c) comprises an ELISA. The invention further provides a kit of parts for use in diagnosing coeliac disease in a patient.

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Nottingham, United Kingdom

Martin Griffin