Probing binding requirements of NAD kinase with modified substrate (NAD) analogues.
Bioorganic & medicinal chemistry letters
confidence
Key findings
Synthesis of NAD analogues that inhibit human and M. tuberculosis NAD kinase; uncharged BAD is most potent competitive inhibitor (K(i)=90 microM).
View source on PubMed (PMID 17258457) ↗
- Population
- In vitro (human and Mycobacterium tuberculosis NAD kinase)
- Dosing
- NAD analogues (K(i)=90 microM for BAD)
- Route
- in vitro
- Blinding
- not_reported
- Controls
- none
- Drug class
- coenzyme
Full abstract
Synthesis of novel NAD(+) analogues that cannot be phosphorylated by NAD kinase is reported. In these analogues the C2' hydroxyl group of the adenosine moiety was replaced by fluorine in the ribo or arabino configuration (1 and 2, respectively) or was inverted into arabino configuration to give compound 3. Compounds 1 and 2 showed inhibition of human NAD kinase, whereas analogue 3 inhibited both the human and Mycobacterium tuberculosis NAD kinase. An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (K(i)=90 microM) of the human enzyme reported so far.