The enzymatic conversion of isothiazolo[4,3-d]pyrimidine-based adenosine ( tz A) and 2-aminoadenosine ( tz 2-AA) analogues to the corresponding isothiazolo[4,3-d]pyrimidine-based inosine ( tz I) and guanosine ( tz G) derivatives is evaluated and compared to the conversion of native adenosine to inosine. Henri–Michaelis–Menten analyses provides the foundation for a high-throughput screening assay, and the efficacy of the assay is showcased by fluorescence-based analysis of tz A conversion to tz I in the presence of known and newly synthesized inhibitors.

Fluorescing Isofunctional Ribonucleosides: Assessing Adenosine Deaminase Activity and Inhibition

Fin A.;
2019

Abstract

The enzymatic conversion of isothiazolo[4,3-d]pyrimidine-based adenosine ( tz A) and 2-aminoadenosine ( tz 2-AA) analogues to the corresponding isothiazolo[4,3-d]pyrimidine-based inosine ( tz I) and guanosine ( tz G) derivatives is evaluated and compared to the conversion of native adenosine to inosine. Henri–Michaelis–Menten analyses provides the foundation for a high-throughput screening assay, and the efficacy of the assay is showcased by fluorescence-based analysis of tz A conversion to tz I in the presence of known and newly synthesized inhibitors.
20
5
718
726
http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1439-7633
adenosine; adenosine deaminase; enzyme catalysis; high-throughput screening; inhibitors; Adenosine Deaminase; Enzyme Inhibitors; Fluorescence; Guanosine; Kinetics; Adenosine; Inosine
Ludford P.T.; Rovira A.R.; Fin A.; Tor Y.
File in questo prodotto:
File Dimensione Formato  
MMChemBioChem.pdf

Accesso riservato

Descrizione: Preprint
Tipo di file: PREPRINT (PRIMA BOZZA)
Dimensione 737.82 kB
Formato Adobe PDF
737.82 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1729363
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact