Design, Synthesis, and Chemical and Biological Properties of Cyclic ADP-4-Thioribose as a Stable Equivalent of Cyclic ADP-Ribose.

Here we describe the successful synthesis of cyclic ADP-4-thioribose (cADPtR, ), designed as a stable mimic of cyclic ADP-ribose (cADPR, ), a Ca-mobilizing second messenger, in which the key N1-β-thioribosyladenosine structure was stereoselectively constructed by condensation between the imidazole nucleoside derivative and the 4-thioribosylamine via equilibrium in between the α-anomer () and the β-anomer () during the reaction course. cADPtR is, unlike cADPR, chemically and biologically stable, while it effectively mobilizes intracellular Ca like cADPR in various biological systems, such as sea urchin homogenate, NG108-15 neuronal cells, and Jurkat T-lymphocytes. Thus, cADPtR is a stable equivalent of cADPR, which can be useful as a biological tool for investigating cADPR-mediated Ca-mobilizing pathways.

Limited lactational transfer of acrylamide to rat offspring on maternal oral administration during the gestation and lactation periods.

To evaluate the developmental exposure effects of acrylamide (ACR) on the nervous and male reproductive systems, pregnant Sprague-Dawley rats were given ACR at 0, 25, 50 or 100 ppm in the drinking water from gestational day 6 to postnatal day (PND) 21 and histopathological assessment was performed at PND 21. Exposure levels in offspring were examined by measurement of free ACR and hemoglobin (Hb)-ACR adducts on PND 14, and compared with maternal levels on PND 21. Additionally, a group of offspring that received ACR at 50 mg/kg by intraperitoneal injections directly three times a week from PND 2 to 21 was subjected to analysis for comparison with maternal exposure groups.

Synthesis of 5''-branched derivatives of cyclic ADP-carbocyclic-ribose, a potent Ca2+-mobilizing agent: The first antagonists modified at the N1-ribose moiety.

The 5''-branched cyclic ADP-carbocyclic-ribose derivatives were designed and synthesized. These target compounds were identified as the first antagonists of cADPR without a substituent at the adenine 8-position, and were shown to be stable due to the N1-carbocyclic-ribosyl structure.

Synthesis of 5''-substituted cyclic ADP-carbocyclic-ribose as biological tools.

5''-Branched cyclic ADP-carbocyclic-riboses (4 and 5) were designed as biological tools for identifying the target proteins of cyclic ADP-ribose, an intracellular Ca(2+)-mobilizing second messenger. One of the targets, 4, successfully synthesized.

Radical reactions with 2-bromobenzylidene group, a protecting/radical-translocating group for the 1,6-radical hydrogen transfer reaction.

[Structure: see text] The 2-bromobenzylidene group, designed as a novel protecting/radical-translocating (PRT) group, proved to be effective for an unusual 1,6-hydrogen transfer reaction. Using this PRT group, 4-branched ribose derivatives were stereoselectively prepared.