NAD kinase (NADK) is a key enzyme that regulates supply of NADP in the cell. At this time no other pathway of NADP biosynthesis has been found in prokaryotic or eukaryotic cells. Human NAD kinase catalyzes a magnesium- dependent phosphorylation of the 2’-hydroxyl group of the adenosine ribose moiety of NAD using ATP as phosphoryl donor to give NADP. Bacterial enzymes can use inorganic polyphosphates as phosphoryl donors in addition to ATP. Significant differences between the human and the mycobacterium enzyme were found that might allow for construction of inhibitors with selectivity against these proteins. Therefore, M. tubercolosis NADK has became an appealing new target for the development of potential drugs against multi-drug resistant (MDR) and extensively drug resistant (XDR) tubercolosis (TB). Recently, we have reported that dinucleoside disulfide NAD mimics, such as diadenosine disulfide (DTA), were found to be moderate inhibitors of M. tubercolosis and human NADKs. A restriction of the conformation of adenine moiety to syn by substitution with a bulky bromine atom at the C8 of one or two adenine rings of DTA, furnished the most potent inhibitors of both human and mycobacterium NADK reported so far. On the contrary, fixing the sugar conformation in the “North” or “South” conformation by introduction of a methyl group at the 2’- or 3’-position of the ribose ring was detrimental for NADK inhibitory activity [1]. To further investigate the structural features of the ribose moiety, herein we report the synthesis and the NADK inhibitory activity of 2’-deoxy-, 3’-deoxy-, and 2’,3’-dideoxy-DTA. The results of this study will be presented. [1] R. Petrelli, Y.Y. Sham, L. Chen, K. Felczak, E. Bennett, D. Wilson, C. Aldrich, J.S. Yu, L. Cappellacci, P. Franchetti, M. Grifantini, F. Mazzola, M. Di Stefano, G. Magni, and K. Pankiewicz, Bioorg. Med. Chem., 17, 2009, 5656.