133728-24-2Relevant academic research and scientific papers
Transposing molecular fluorescent switches into the near-IR: Development of luminogenic reporter substrates for redox metabolism
Halim, Marlin,Tremblay, Matthew S.,Jockusch, Steffen,Turro, Nicholas J.,Sames, Dalibor
, p. 7704 - 7705 (2007)
This study reports the development of a Nd(III)-based near-IR luminescent probe for monitoring aldo-ketoreductase (AKR) enzyme activity. We have adapted a coumarin-based reporter substrate for the AKR1C2 to a near-IR emitting format by tethering the former to a macrocyclic Nd(III) moiety via an alkyl linker. Enzymatic reduction of the ketone functionality on the coumarin alters the energy transfer efficiency from the fluorophore to the emitting lanthanide species, resulting in emission at ～1060 nm from the alcohol product. The efficiency of sensitization is not significantly affected by extending the alkyl tether from two to three carbons, and even a six-carbon linker still supports viable sensitized luminescence. In addition, the suitability of these complexes to act as enzyme substrates improves with longer linker length. We have thus developed long wavelength luminogenic reporter substrates for a redox enzyme and also a general platform for transposing molecular fluorescence into the more desirable near-IR region. Copyright
Thiol-based potent and selective HDAC6 inhibitors promote tubulin acetylation and T-regulatory cell suppressive function
Segretti, Mariana C. F.,Vallerini, Gian Paolo,Brochier, Camille,Langley, Brett,Wang, Liqing,Hancock, Wayne W.,Kozikowski, Alan P.
, p. 1156 - 1161 (2015)
Several new mercaptoacetamides were synthesized and studied as HDAC6 inhibitors. One compound, 2b, bearing an aminoquinoline cap group, was found to show 1.3 nM potency at HDAC6, with >3000-fold selectivity over HDAC1. 2b also showed excellent efficacy at increasing tubulin acetylation in rat primary cortical cultures, inducing a 10-fold increase in acetylated tubulin at 1 μM. To assess possible therapeutic effects, compounds were assayed for their ability to increase T-regulatory (Treg) suppressive function. Some but not all of the compounds increased Treg function, and thereby decreased conventional T cell activation and proliferation in vitro.
BICYCLIC AND TRICYCLIC CAP BEARING MERCAPTOACETAMIDE DERIVATIVES AS HISTONE DEACETYLASE INHIBITORS
-
Paragraph 0212; 0213, (2017/04/11)
Histone deacetylases inhibitors (HDACIs) and compositions containing the same are disclosed. Methods of treating diseases and conditions wherein inhibition of HDAC provides a benefit, like a cancer, a neurodegenerative disorder, a peripheral neuropathy, a neurological disease, traumatic brain injury, stroke, hypertension, malaria, an autoimmune disease, autism, autism spectrum disorders, and inflammation, also are disclosed.
Site-specific chemoenzymatic protein modifications
-
Page/Page column 73; 74, (2016/06/28)
The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.
HDAC INHIBITORS
-
Page/Page column 30; 31, (2009/04/25)
The present invention provides hydroxamic acid compounds, and methods of preparation of these compounds. The present invention also relates to pharmaceutical compositions comprising the hydroxamic acid compounds. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a compound of the present invention.
Improving broad specificity hapten recognition with protein engineering.
Korpimaeki, Teemu,Rosenberg, Jaana,Virtanen, Pekka,Karskela, Tuomas,Lamminmaeki, Urpo,Tuomola, Mika,Vehniaeinen, Markus,Saviranta, Petri
, p. 4194 - 4201 (2007/10/03)
Sulfa antibiotics (sulfonamides) are derivatives of p-aminobenzenesulfonamide that are widely used in veterinary medicine. Foods derived from treated animals may be contaminated with these drugs. However, current immunobased sulfonamide detection methods are unfit for screening of products because they are either too insensitive or specific for a few compounds only. An immunoassay capable of detecting all sulfas in a single reaction would be ideal for screening. For development of a binder capable of binding all sulfas, a protein engineering approach was chosen and the properties of monoclonal antibody 27G3 were improved with mutagenesis followed by selection with phage display. Several different mutant antibodies were isolated. The cross-reaction profile of the best mutant antibody was significantly improved over that of the wild-type antibody: it was capable of binding 9 of the tested 13 sulfonamides within a narrow concentration range and also bound the rest of the sulfas, albeit within a wider concentration range.
