rp-camps sodium

Rp-8-CPT-cAMP is a structural combination of the lipophilic and non-hydrolyzable cAMP analogs, 8-CPT-cyclic AMP and Rp-cyclic AMPS .[1] It functions as a site-selective inhibitor of protein kinase A (PKA) type I and II, with preference towards site A of type I and site B of type II.2 By occupying cAMP binding sites at the regulatory subunit of PKA, Rp-8-CPT-cAMP prevents the kinase holoenzyme from dissociative activation.[2],[3]

Rp-cAMPS sodium salt, a cAMP analog, is a potent, competitive cAMP-induced activation of cAMP-dependent PKA I and II (Kis of 12.5 μM and 4.5 μM, respectively) antagonist. Rp-cAMPS sodium salt is resistant to hydrolysis by phosphodiesterases[1][2][3][4][5][6]. A membrane-permeable competitive cAMP antagonist (Rp-cAMPS) that blocks PKA activation by binding to the regulatory subunits without dissociating the kinase holoenzyme also inhibits synaptic plasticity but has no effect on normal synaptic transmission[2]. Rp-cAMPS (10 μM, 15 min) decreases the monosynaptic EPSCs evoked at the PB-CeLC and BLA-CeLC synapses in slices from arthritic rats but not in control neurons from normal animals. The inhibitory effect of Rp-cAMPS is significant compared to predrug (ACSF) control values obtained in the same neurons[2]. [1]. R J de Wit, et al. Inhibitory action of certain cyclophosphate derivatives of cAMP on cAMP-dependent protein kinases. Eur J Biochem. 1984 Jul 16;142(2):255-60. [2]. Rothermel JD, et al. A mechanistic and kinetic analysis of the interactions of the diastereoisomers of adenosine 3’,5’-(cyclic)phosphorothioate with purified cyclic AMP-dependent protein kinase. Biochem J. 1988 May 1;251(3):757-62.[3]. Fu Y, et al. PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior. Mol Pain. 2008 Jul 16;4:26.[4]. Kuriyama S, et al. Isoproterenol inhibits rod outer segment phagocytosis by both cAMP-dependent and independent pathways. Invest Ophthalmol Vis Sci. 1995 Mar;36(3):730-6.[5]. Dostmann WR, et al. Probing the cyclic nucleotide binding sites of cAMP-dependent protein kinases I and II with analogs of adenosine 3’,5’-cyclic phosphorothioates. J Biol Chem. 1990 Jun 25;265(18):10484-91.[6]. Van Haastert PJ, et al. Competitive cAMP antagonists for cAMP-receptor proteins. J Biol Chem. 1984 Aug 25;259(16):10020-4.

Rp-cAMPS competitively inhibits the cAMP-induced activation of cAMP-dependent protein kinase (PKA).

Rp-Uridine-5'-O-(1-thiotriphosphate) (Rp-UTP-α-S) serves as a nucleotide agonist for purinergic P2Y2 and P2Y4 receptors, effectively inducing inositol phosphate accumulation within 1321N1 astrocytoma cells that express either P2Y2 or P2Y4 receptors, with EC50 values of 5.4 and 27 µM, respectively.

Rp-2'-Deoxyuridine-5'-O-(1-thiotriphosphate) (Rp-dUTP-α-S), a sulfur-containing nucleotide isomer and purinergic P2Y2 receptor agonist, preferentially promotes inositol phosphate accumulation in 1321N1 astrocytoma cells with P2Y2 receptors (EC50 = 12.5 µM) compared to those expressing P2Y4 receptors at a concentration of 10 µM.

Rp-cAMPS triethylammonium salt is an analog of cAMP.It acts as a potent, competitive and cell-permeable antagonist of cAMP-induced activation of cAMP-dependent PKA I and II with Kis of 6.05 µM and 9.75 µM, respectively.

Rp-Adenosine-5'-O-(1-thiotriphosphate) (Rp-ATP-α-S), a sulfur-containing nucleotide derivative isomer and a purinergic P2Y1 receptor agonist, promotes calcium mobilization in HEK293 cells expressing the human P2Y1 receptor (EC50 = 75 nM). This compound exhibits binding affinity to washed isolated human platelets (Ki = 156 nM) and attenuates ADP-induced aggregation in human platelet-rich plasma (PRP; pA2 = 4.74), as well as inhibits cAMP production triggered by prostaglandin E1 (PGE1) in human PRP (pA2 = 5.26). Furthermore, it triggers relaxation in carbamoylcholine-constricted guinea pig taenia coli strips (EC50 = 56 nM). Rp-ATP-α-S also contributes to the synthesis of cyclic dinucleotides, recognized by bacterial riboswitches.

Rp-8-CPT-cAMPS is a powerful and competitive antagonist of cAMP-induced activation of cAMP-dependent protein kinase (PKA) I and II. Acting as a potent cAMP analog, Rp-8-CPT-cAMPS exhibits a preference for site A of RI over site A of RII. Additionally, it favors site B of RII over site B of RI. This compound effectively inhibits cAMP-dependent PKA activation and demonstrates selectivity in binding to specific sites within the protein kinase.

Rp-8-bromo-Cyclic AMPS (Rp-8-bromo-cAMPS) is a cell-permeable cAMP analog that combines an exocyclic sulfur substitution in the equatorial position of the cyclophosphate ring with a bromine substitution in the adenine base of cAMP. It acts as an antagonist of cAMP-dependent protein kinases (PKAs) and is resistant to hydrolysis by cyclic nucleotide phosphodiesterases. Rp-8-bromo-cAMPS more effectively antagonizes cAMP-dependent activation of purified PKA type I from rabbit muscle than PKA type II from bovine heart.

Rp-Adenosine-5'-O-(1-thiodiphosphate) (Rp-ADP-α-S), a sulfur-containing isomer of the nucleotide derivative ADP-α-S, acts as an inhibitor of phosphorylase kinase with an inhibition constant (Ki) of 0.53 µM. This compound also induces aggregation in isolated human platelets with an effective concentration (EC50) of 20 µM and promotes relaxation in guinea pig taenia coli that has been precontracted with carbamoylcholine, with an EC50 of 58.9 µM.

Rp-Thymidine-5'-O-(1-thiotriphosphate) (Rp-TTP-α-S), an isomer of the sulfur-containing nucleotide derivative TTP-α-S, selectively interacts with HIV-1 reverse transcriptase, exhibiting dissociation constants (Kds) of 45.7, 27.32, and 39.44 µM in the presence of magnesium, manganate, and cobalt, respectively.