In:
ChemBioChem, Wiley, Vol. 18, No. 16 ( 2017-08-17), p. 1616-1626
Abstract:
The design of a bioreversibly protected lipophilic sugar nucleotide as a potential membrane‐permeable precursor of adenosine diphosphate ribose (ADPR) is described. ADPR is the most potent activator of the transient receptor potential melastatin 2 (TRPM2) ion channel. Membrane‐permeable, lipophilic derivatives of ADPR are of great interest as tools for study of the mechanism of TRPM2. The approach described here was based on our recently disclosed “Di PP ro” and “Tri PPP ro” prodrug approaches developed for the intracellular delivery of nucleotides. A lipophilic, bioreversibly masked ADPR analogue containing an enzymatically cleavable 4‐pentanoyloxybenzyl (PB) mask at the phosphate moiety next to the 5′‐position of adenosine, together with O‐acetyl groups, was prepared in high yields. Chemical and enzymatic hydrolysis studies in phosphate buffer (pH 7.3) were performed to assess chemical stability and possible (selective) enzymatic demasking of the ADPR analogue. HPLC‐MS revealed that the PB group was readily cleaved enzymatically. In addition, the formation of partially deacetylated ADPR compounds and also of fully unprotected ADPR was observed.
Type of Medium:
Online Resource
ISSN:
1439-4227
,
1439-7633
DOI:
10.1002/cbic.201700232
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2020469-3
SSG:
12
