2382-65-2

Usage

Uses

Used in Pharmaceutical Industry:
CYTIDYLYL-(3'->5')-GUANOSINE is used as a signaling molecule for its role in regulating various physiological functions, including blood pressure, smooth muscle relaxation, and neurotransmission. Its involvement in cell growth, differentiation, and apoptosis makes it a potential target for the development of therapeutic agents.
Used in Research Applications:
CYTIDYLYL-(3'->5')-GUANOSINE is used as a research tool for studying the cGMP-dependent protein kinase (PKG) signaling pathway and its impact on cellular processes. It aids in understanding the molecular mechanisms underlying various physiological functions and the development of potential therapeutic strategies.
Used in Diagnostic Applications:
CYTIDYLYL-(3'->5')-GUANOSINE is used as a biomarker for monitoring the activity of the cGMP-dependent protein kinase (PKG) signaling pathway in various diseases and conditions. Its measurement can provide insights into the underlying pathophysiology and help in the development of targeted therapies.
Used in Drug Development:
CYTIDYLYL-(3'->5')-GUANOSINE is used as a target for the development of drugs that modulate the cGMP-dependent protein kinase (PKG) signaling pathway. These drugs can potentially treat a range of diseases and conditions by regulating cellular processes such as cell growth, differentiation, and apoptosis.

Upstream product

• 22886-38-0 Phosphoric acid (2R,3S,4R,5R)-5-(2-amino-6-oxo-1,6-dihydro-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-ylmethyl ester (2R,3R,4R,5R)-2-(4-amino-2-oxo-2H-pyrimidin-1-yl)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-3-yl ester 

Downstream Products

• 633-90-9 cytidine 2',3'-cyclic monophosphate 
• 84-52-6 cytidine 3'-monophosphate 
• 85-94-9 cytidine-2'-monophosphate 
• 118-00-3 G 

Relevant academic research and scientific papers

Kinetic analysis of the cleavage of the ribose phosphodiester bond within guanine and cytosine-rich oligonucleotides and dinucleotides at 65-200 °C and its implications concerning the chemical evolution of RNA

A monitoring method of rapid hydrothermal reactions was successfully applied to a kinetic analysis of the cleavage of a ribose phosphodiester bond within oligonucleotides and dinucleotides at 150-200 °C. The apparent rate constants (kapp) of degradation of the ribose 3′,5′-cytidylylguanosine sequence (-C3′pGd-) within oligonucleotides and dinucleotides were determined, where the -C3′pGd- sequence in oligonucleotides is less stable than 2′,5′-cytidylylguanosine (C2′pG) and 3′,5′-cytidylylguanosine (C3′pG). It was unexpected that the stability of the target sequence would be dependent on the surrounding sequences of the oligonucleotides, although the temperatures used in the study were extremely higher than the melting points. The stability of a phosphodiester bond of 2′-deoxycytidylyl-2′-deoxyguanosine (CdpGd) is much higher than that of a ribose phosphodiester bond at low temperatures, but becomes comparable at 200 °C. During the degradation of C2′pG or C3′pG, interconversion between C2′pG and C3′pG was observed along with cleavage of the phosphodiester bond. Based on an analysis of the extent of interconversion, the apparent rate constants of the disappearance of C2′pG and C3′pG were dissected into the rate constants of hydrolysis (khy) and interconversion (kint), where the values of khy were greater than those of kint. The apparent activation energy of the degradation of the target sequence was 100-109 kJ mol-1 for oligonucleotides, 90 kJ mol-1 for C3′pG, and 87 kJ mol-1 for C2′pG, and 139 kJ mol-1 for CdpGd. The apparent activation enthalpy and entropy changes of the degradation of the target sequence were also determined; the values of the activation parameter were ΔHapp = 94-105 kJ mol-1 and ΔSapp= -(36-59) J mol-1 T-1 for five oligonucleotides, ΔHapp = 86 kJ mol-1 and ΔSapp = -97 J mol-1 T-1 for C3′pG, ΔHapp = 84 kJ mol-1, ΔXSapp = - 105 J mol-1 T-1 for C2′pG, and ΔHapp = 135 kJ mol-1, ΔSapp = +2 J mol-1 T-1 for CdpGd. The activation parameters, ΔHapp and ΔSapp, for the oligonucleotides increased with the length of the surrounding sequence of -C3′pGd-; this fact clearly demonstrates the existence of the influence of the surrounding sequence for the stability of the target ribose phosphodiester bond. Based on a kinetic analysis, the reaction mechanism of the degradation of the ribose phosphodiester bond at high temperatures is discussed. Furthermore, possible pathways of the chemical evolution of RNA are discussed from the viewpoint of the hydrothermal origin of life.

Synthesis of 1'%,2',3',4'%,5',5"-(2)H6-β-D-ribonucleosides and 1'%,2',2",3',4'%,5',5"-(2)H7-β-D-2'-deoxyribonucleosides for Selective Suppression of Proton Resonances in Partially-deuterated Oligo-DNA, Oligo-RNA and in 2,5A core ((1)H-NMR window)

Raney nickel-(2)H2O exchange reaction on an epimeric mixture of methyl α/β-D-ribofuranoside 1 produced methyl 1%,2,3,4%,5,5'-(2)H6-α/β-D-ribofuranoside 2 ( >97 atom percent (2)H at C2, C3, C5/5'; ca. 85 atom percent (2)H at C4(C4%); ca. 20 atom percent (2)H at C1(C1%)) which was obtained in 60 - 80percent yield along with epimeric xylo and arabino by-products.Toluoylation of the crude 2 in dry pyridine and a careful separation on a column of silica gel gave pure 1-O-methyl-2,3,5-tri-O-(4-toluoyl)-α/β-D-1%,2,3,4%,5,5'-(2)H6-ribofuranoside 4 (48percent).Conversion of 4 to1-O-acetyl-2,3,5-tri-O-toluoyl-α/β-D-1%,2,3,4%,5,5'-(2)H6-ribofuranoside 6 (82percent) provided the crucial building block for the synthesis of deuterionucleosides for RNA or DNA synthesis.Compound 6 was then condensed with silyated uracil, N4-benzoylcytosine, N6-benzoyladenine, N2-acetyl-O6-diphenylcarbamoylguanine and thymine in anhydrous solvent using trimethylsilyl trifluoromethanesulfonate to give the corresponding isomerically pure 1'%,2',3',4'%,5',5"-(2)H6-ribonucleoside derivatives 7, 8, 9, 10, 11 in 75, 85, 60, 73 and 91percent yields, respectively. 1'%,2',3',4'%,5',5"-(2)H6-ribonucleosides 13-16 were converted in high yields to the corresponding 1'%,2',2",3',4'%,5',5"-(2)H7-2'-deoxynucleosides 41-44 in the following manner: 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl (TPDS)-1'%,2',3',4'%,5',5"-(2)H6-nucleosides 29-32 were converted to the corresponding 2'-O-phenoxythiocarbonyl derivatives 33-36, which were deoxygenated by tri-n-butyltin deuteride to give 1'%,2',2",3',4'%,5',5"-(2)H7-2'-deoxynucleosides 37-40 and subsequently deprotected to give 41-44.Pure 1'%,2',3',4'%,5',5"-(2)H6-ribonucleoside derivatives 12-15, 1'%,2',2",3',4'%,5',5"-(2)H7-2'-deoxynucleoside blocks 41-44 and their natural-abundance counterparts were then used to assemble partially deuterated ribonucleotide-dimers (* indicates deuterated moiety): UpA* 77, CpG* 78, ApU* 79, GpC* 80, partially deuterated 2'-deoxyribonucleotide-dimers d(TpA*) 93, d(CpG*) 94, d(ApT*) 95, d(GpC*) 96 and partially deuterated 2,5A core (A*2'p5'A2'p5'A*) (109).These nine partially deuterated oligonucleotides were subsequently compared with their corresponding natural-abundance counterparts by 500 MHz (1)H-NMR spectroscopy to evaluate the actual NMR simplifications achieved in the non-deuterated part ((1)H-NMR window) as a result of specific deuterium incorporation.Detailed 1D (1)H-NMR (500 MHz), 2D correlation spectra (DQF-COSY and TOCSY), T1 measurements for (1)H-, (13)C- and INEPT (13)C-NMR spectra have been presented and discussed to assess the utility of stereospecific deuterium incorporation to create the (1)H- or (13)C-NMR window.