Emissive Synthetic Cofactors: Enzymatic Interconversions of ^tzA Analogues of ATP, NAD⁺, NADH, NADP⁺, and NADPH

Abstract

As eries of enzymatic transformations,w hich generate visibly emissive isofunctional cofactors based on an isothiazolo [4,3-d]pyrimidine analogue of adenosine ( tz A), was developed. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and tz ATP to yield N tz AD + ,w hich can be enzymatically phosphorylated by NAD + kinase and ATPor tz ATP to the corresponding N tz ADP + .The latter can be engaged in NADP-specific coupled enzymatic transformations involving conversion to N tz ADPH by glucose-6-phosphate dehydrogenase and reoxidation to N tz ADP + by glutathione reductase.The N tz ADP + /N tz ADPH cycle can be monitored in real time by fluorescence spectroscopy. Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.201711935. tz A: isothiazolo[4,3-d]pyrimidine analogue of adenosine. Scheme 1. Synthesis of tz ATP.i )POCl 3 ,( MeO) 3 PO, 0 8 8Ct ort, 2h; ii)tributylammonium pyrophosphate, Bu 3 N, 0 8 8Ct ort, 2h,20%. Angewandte Chemie Communications Conflict of interestProfessor Torp rovides consulting services to Tr iLink Biotechnologies.T he terms of the arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.

The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae

“…This is illustrated by Inosine-50 -monophosphate dehydrogenase (IMPDH cofactor) that interacts with three different binding domains, namely (a) nicotinamide binding subsite (N-subsite), (b) adenosine binding subsite (A-subsite), and (c) pyrophosphate binding subsite (P-subsite) (Felczak eand Pankiewicz 2011 ; Pankiewicz and Felczak 2015 ). Also, significant advances have been made in exploiting enzymes involved in natural product biosynthesis and new structure bearing non-natural substituents (Wang et al 2017 ), as witness in the rising implementation and their application in chemical and synthetic biology (Rovira et al 2017 ; Halle et al 2018 ; Wang et al 2021 ).…”