Recent advances in the development of tissue transglutaminase (TG2) inhibitors


Tissue transglutaminase (TG2) is a Ca2+-dependent enzyme and probably the most ubiquitously expressed member of the mammalian transglutaminase family. TG2 plays a number of important roles in a variety of biological processes. Via its transamidating function, it is responsible for the cross-linking of proteins by forming isopeptide bonds between glutamine and lysine residues. Intracellularly, Ca2+ activation of the enzyme is normally tightly regulated by the binding of GTP. However, upregulated levels of TG2 are associated with many disease states like celiac sprue, certain types of cancer, fibrosis, cystic fibrosis, multiple sclerosis, Alzheimer's, Huntington's and Parkinson's disease. Selective inhibitors for TG2 both cell penetrating and non-cell penetrating would therefore serve as novel therapeutic tools for the treatment of these disease states. Moreover, they would provide useful tools to fully elucidate the cellular mechanisms TG2 is involved in and help comprehend how the enzyme is regulated at the cellular level. The current paper is intended to give an update on the recently discovered classes of TG2 inhibitors along with their structure-activity relationships. The biological properties of these derivatives, in terms of both activity and selectivity, will also be reported in order to translate their potential for future therapeutic developments. © 2011 Springer-Verlag.

Publication DOI:
Divisions: College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
Aston University (General)
Uncontrolled Keywords: inhibitors,structure-activity relationships (SAR),TG2,tissue transglutaminase,Biochemistry,Clinical Biochemistry,Organic Chemistry
Publication ISSN: 1438-2199
Last Modified: 15 Apr 2024 07:10
Date Deposited: 19 Aug 2019 08:53
Full Text Link: http://www.spri ... 8q91770m3060wx/
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2013-01
Published Online Date: 2011-12-13
Authors: Badarau, Eduard
Collighan, Russell J. (ORCID Profile 0000-0003-0204-5125)
Griffin, Martin (ORCID Profile 0000-0003-3824-306X)



Version: Accepted Version

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