O-ADP-Ribosylation in the NAD/NADase System: 2-Alkanols as Efficient Substrates.

Abstract

Several 2-alkanols (2-propanol, 2-butanol, 2-pentanol, etc.) were examined as substrates for ADP-ribosylation in the NAD/NADase enzymatic system. Even though these secondary alcohols have hydroxy groups that are subject to the steric influence of a methyl group, they were shown to be efficiently ADP-ribosylated. However, in the case of 3-alkanol (3-butanol), only slight ADP-ribosylation was observed. In this enzymatic reaction, 1,2-propanediol provided both 1-O-and 2-O-ADP-ribosylation products in the ratio 1 : 1 as determined by 1 H-NMR spectrometry. On the other hand, an equimolar mixture system of 1-and 2-propanols provided major 1-O-and minor 2-O-ribosylation products in the ratio 4 : 1. This is the first report of O-ADP-ribosylation of terminal secondary alcohols with the NAD/NADase enzymatic system.

SIR2: The Biochemical Mechanism of NAD+-Dependent Protein Deacetylation and ADP-Ribosyl Enzyme Intermediates

“…CD38/NAD + glycohydrolases catalyze ADPR transfer to a variety of relatively weak nucleophiles including 2º alcohols [62]. This indiscriminate reactivity is consistent with the oxacarbenium ion transition state structures proposed for ADPR transfer for this enzyme [49,54,58,59].…”

A Colorimetric Substrate for Poly(ADP‐Ribose) Polymerase‐1, VPARP, and Tankyrase‐1

“…The use of commercially available β‐NAD + as a starting material would greatly simplify the synthesis of this substrate. Very little literature precedent exists for the chemical modification of NAD + ; basic methanolysis is possible and yields a 3.7:1 mixture of β/α anomers,32 whereas methods employing the NADase/NAD + enzymatic system provide N‐ and O‐ (ADP‐ribosyl)ation products, albeit in low yield and limited substrate scope 33–35. As syntheses of cyclic ADP‐ribose analogues have utilized nucleophilic metal halides in the presence of triethylamine to successfully and stereoselectively cyclize NAD + ,36 this strategy was adopted in the preparation of ADP‐ribose‐ p NP, 1 .…”