28683-92-3Relevant articles and documents
Allosterically Regulated Phosphatase Activity from Peptide–PNA Conjugates Folded Through Hybridization
Machida, Takuya,Dutt, Som,Winssinger, Nicolas
, p. 8595 - 8598 (2016)
The importance of spatial organization in short peptide catalysts is well recognized. We synthesized and screened a library of peptides flanked by peptide nucleic acids (PNAs) such that the peptide would be constrained in a hairpin loop upon hybridization. A screen for phosphatase activity led to the discovery of a catalyst with >25-fold rate acceleration over the linear peptide. We demonstrated that the hybridization-enforced folding of the peptide is necessary for activity, and designed a catalyst that is allosterically controlled using a complementary PNA sequence.
FLUOROGENIC BETA-LACTAMASE SUBSTRATE AND ASSOCIATED DETECTION METHOD
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Page/Page column 40, (2021/06/04)
This invention relates to probes for the detection of β-lactamase-type enzymatic activity. In particular, the invention relates to novel fluorogenic substrates for detecting the presence of a catalytically active β-lactamase and a detection method using such substrates.
Selective, Modular Probes for Thioredoxins Enabled by Rational Tuning of a Unique Disulfide Structure Motif
Becker, Katja,Busker, Sander,Felber, Jan G.,Maier, Martin S.,Poczka, Lena,Scholzen, Karoline,Theisen, Ulrike,Thorn-Seshold, Julia,Thorn-Seshold, Oliver,Zeisel, Lukas,Arnér, Elias S. J.,Brandst?dter, Christina
supporting information, p. 8791 - 8803 (2021/06/27)
Specialized cellular networks of oxidoreductases coordinate the dithiol/disulfide-exchange reactions that control metabolism, protein regulation, and redox homeostasis. For probes to be selective for redox enzymes and effector proteins (nM to μM concentrations), they must also be able to resist non-specific triggering by the ca. 50 mM background of non-catalytic cellular monothiols. However, no such selective reduction-sensing systems have yet been established. Here, we used rational structural design to independently vary thermodynamic and kinetic aspects of disulfide stability, creating a series of unusual disulfide reduction trigger units designed for stability to monothiols. We integrated the motifs into modular series of fluorogenic probes that release and activate an arbitrary chemical cargo upon reduction, and compared their performance to that of the literature-known disulfides. The probes were comprehensively screened for biological stability and selectivity against a range of redox effector proteins and enzymes. This design process delivered the first disulfide probes with excellent stability to monothiols yet high selectivity for the key redox-Active protein effector, thioredoxin. We anticipate that further applications of these novel disulfide triggers will deliver unique probes targeting cellular thioredoxins. We also anticipate that further tuning following this design paradigm will enable redox probes for other important dithiol-manifold redox proteins, that will be useful in revealing the hitherto hidden dynamics of endogenous cellular redox systems.
Optically-Detectable Enzyme Substrates and Their Method of Use
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, (2016/06/06)
The present invention relates to compounds that are substrates for an enzyme, and upon reaction with the enzyme provide a detectable response, such as an optically detectable response. In particular, the compounds have utility in detecting the presence of a β-lactamase in a sample. In addition to the compounds, methods are disclosed for analyzing a sample for the presence of a β-lactmase, for example, as an indicator of expression of a nucleic acid sequence including a sequence coding for a β-lactmase. Kits are disclosed that include the disclosed compounds and additional components, for example, cells, antibodies, a β-lactmase or instructions for using the components in an assay.
QUINAZOLINONE BASED FLUOROGENIC PROBES
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Page/Page column 9; 10, (2012/12/13)
The present invention relates to a compound of the general formula (I) useful in the determining the presence, amount or activity of an enzyme in living cells, a method of preparing said compounds and a kit thereof.
Synthesis and characterization of 2-(2′-hydroxy-5′- chlorophenyl)-6-chloro- 4(3H)-quinazolinone-based fluorogenic probes for cellular imaging of monoamine oxidases
Aw, Junxin,Shao, Qing,Yang, Yanmei,Jiang, Tingting,Ang, Chungyen,Xing, Bengang
supporting information; experimental part, p. 1317 - 1321 (2011/08/02)
Monoamine oxidases (MAOs) catalyze the oxidative deamination of neuro-transmitters and biogenic amines. A new class of activity-based fluorescent probes based on the alkylation of 2-(2'-hydroxyphenyl)-4(3 H)-quinazolinone (HPQ) with primary, secondary, or
Fluorescent molecular probes I. The synthesis and biological properties of an ELF β-glucuronidase substrate that yields fluorescent precipitates at the enzymatic activity sites
Diwu, Zhenjun,Lu, Yixin,Upson, Rosalyn H.,Zhou, Mingjie,Klaubert, Dieter H.,Haugland, Richard P.
, p. 7159 - 7164 (2007/10/03)
A novel quinazolinone-based fluorogenic β-glucuronidase substrate has been synthesized and evaluated. In this protocol, a partially protected salicyl glucuronide is oxidatively condensed with anthranilamide to afford the required quinazolinonyl glucuronic acid methyl ester that is readily deprotected to yield the desired glucuronide, known as ELF-97 glucuronide. The glucuronide is a sensitive fluorogenic β-glucuronidase substrate that yields a bright yellow-green fluorescent precipitate upon enzymatic reaction.
Synthesis and use of new fluorogenic precipitating substrates
Naleway, John J.,Fox, Christina M. J.,Robinhold, Daniel,Terpetschnig, Ewald,Olson, Nels A.,Haugland, Richard P.
, p. 8569 - 8572 (2007/10/02)
New fluorogenic esterase, glycosidase, aryl sulfatase, microsomal dealkylase, guanidinobenzoatase and alkaline phosphatase substrates have been prepared which precipitate at the site of enzyme activity, both in vitro and in vivo.
