Nucleotides in Signal Transduction

Ligands for P2 Receptors

Extracellular purine and pyrimidine nucleotides modulate the function of diverse mammalian cell types and tissues under both normal and pathophysiological conditions via corresponding purine and pyrimidine receptors such as the P2 receptor family.

Members of the P2 receptors can be divided into ligand-gated ion channels (P2X receptors) and G-protein-coupled receptors (P2Y receptors), respectively.

Purinergic P2X receptors as ligand-gated cation channels are activated by endogenous ATP and assemble as homo- and hetero-trimers from seven cloned subtypes: P2X1, P2X2, P2X3, P2X4, P2X5, P2X6, and P2X7. From the family of P2Y receptors whose signaling is mediated through coupling to G-proteins, mainly Gqu/11 (P2Y10, P2Y13) and Gi/o (P2Y14), eight mammalian subtypes are known: P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14.

Generally, P2-receptors have been linked to participation in several diseases such as cancer, cardiovascular, inflammatory and neuropathic diseases, including neuropathic pain. Thus, agonist and antagonist ligands for these receptors have a high potential for clinical applications.

We offer different mono- and dinucleotide agonist and antagonist ligands for functional studies of P2X and P2Y subtypes.

Nucleotides Cat. No. Receptor type
ATP NU-1010 P2Y1, P2Y2, P2Y4, hP2Y6, P2Y11, P2X1-7
NPE-caged ATP NU-301 release technology: P2Y1, P2Y2, P2Y4, hP2Y6, P2Y11, P2X1-7
DMB-caged ATP NU-309 release technology: P2Y1, P2Y2, P2Y4, hP2Y6, P2Y11, P2X1-7
ATP-γS NU-406 P2Y2, P2Y12; enzymatic stable
ATP-αS NU-408 P211; enzymatic stable
ApCpp NU-421 P2 – purinoreceptor
AppCp NU-422 P2X – purinoreceptor
AppNHp NU-407 P2Y2
NPE-caged AppNHp NU-305 P2Y2; release technology
Mant-AppNHp NU-214 P2Y2; release technology
8-[(6-Amino)hexyl]-amino-ATP NU-807 P2Y
8-Bromo-ATP NU-997 P2Y2, P2X
Etheno-ATP NU-1103 P2Y
N 6 -Methyl-ATP NU-1101 P2Y, P2X2
AP4U NU-528 P2Y2, P2Y4, P2X1
TNP-ATP NU-221 P2X1-4, P2X
BzBzATP NU-1620 P2X7
ADP NU-1198 P2Y1, hP2Y6, P2Y12, P2Y13
GTP-γS NU-412 P2Y12, P2Y13
CTP NU-1011 P2X3, P2Y6
UTP NU-1013 P2X1, P2Y2
2-Thio-UTP NU-1151 P2Y2, P2Y4, P2Y6
4-Thio-UTP NU-1156 P2Y2, P2Y4
5-Bromo-UTP NU-121 P2Y2, P2Y4
UTP-γS NU-416 P2Y2, P2Y4; enzymatically stable
AP4U NU-528 P2Y2, P2Y4, P2X1
UDP NU-1206 Agonist: hP2Y6; competitive antagonist: P2Y14
3-Phenacyl-UDP NU-1183 Agonist: P2Y6, P2Y2, P2Y4
5-Iodo-UDP NU-867 Agonist: P2Y6
UDPβS NU-442 P2Y6
ITP NU-1203 P2Y2, P2Y4
AP3A NU-506 P2Y1, P2Y12, P2Y13, P2X1-4
AP4A NU-507 P2Y1, P2Y2, P2Y11
AP5A NU-508 P2Y1,2,4,12, P2X1, vascular P2X receptors

Selected References

Jacobson (2013) Structure based approaches to ligands for G-protein-coupled adenosine and P2Y receptors, from small molecules to nanoconjugates. J. Med. Chem. 56:3749.
Jacobson et al. (2009) Development of selective agonists and antagonists of P2Y receptors. Purinergic Signalling 5:75.
Jacobson et al. (2003) Engineering of A3 Adenosine and P2Y Nucleotide Receptors and their ligands. Drug Development Res. 58:330.
Jacobson (2001) Probing adenosine and P2 receptors: design of novel purines and nonpurines as selective ligands. Drug Development Res. 52:178.
Mueller (2002) P2-pyrimidinergic receptors and their ligands. Current Pharmaceutical Design 8:2353.
Volonte et al. (2009) Membrane components and purinergic signalling: the purinome, a complex interplay among ligands, degrading enzymes, receptors and transporters. FEBS J. 276:318.

Bacterial Second Messenger

(p)ppGpp (collective for ppGpp and pppGpp) is a nucleotide based second messenger and a key regulator of stringent stress response in many bacteria[1]. During nutritional starvation (p)ppGpp initiates the switch from bacterial growth into survival mode. Growth is arrested as (p)ppGpp binds RNA polymerase (RNAP) leading to repressed transcription rate of stable RNA (rRNA, tRNA). Instead, transcription of genes involved in biosynthesis of amino acids is enhanced, leading to prolonged survival[2].

Name Cat. No. Size
Guanosine-3’,5′-bisdiphosphate NU-884S 10 μl (100 mM)
Guanosine-3’,5′-bisdiphosphate NU-884L 5 x 10 μl (100 mM)
Guanosine-3’,5′-pentaphosphat NU-885S 10 μl (100 mM)
Guanosine-3’,5′-pentaphosphat NU-885L 5 x 10 μl (100 mM)
cyclic-di-GMP NU-951S 1 μmol
cyclic-di-GMP NU-951L 5 x 1 μmol
AP3A – Solution NU-506S 50 μl (10 mM)
AP3A – Solution NU-506L 5 x 50 μl (10 mM)
AP3A – Solid NU-506-5 5 mg
AP3A – Solid NU-506-25 25 mg
AP4A – Solution NU-507S 100 μl (10 mM)
AP4A – Solution NU-507L 5 x 100 μl (10 mM)
AP4A – Solid NU-507-5 5 mg
AP4A – Solid NU-507-25 25 mg
AP3G (A cap) NU-941-1 1 mg
AP3G (A cap) NU-941-5 5 mg
AP4G NU-503S 50 μl (10 mM)
AP4G NU-503L 5 x 50 μl (10 mM)
cyclic-di-AMP NU-954S 1 μmol
cyclic-di-AMP NU-954L 5 x 1 μmol
3’,3′-cGAMP NU-986S 1 μmol
3’,3′-cGAMP NU-986L 5 x 1 μmol
2’,3′-cGAMP NU-249S 1 μmol
2’,3′-cGAMP NU-249L 5 x 1 μmol

Selected References

[1] Hauryliuk et al. (2015) Recent functional insights into the role of (p)ppGpp in bacterial physiology. Nature Reviews Microbiology 13 (5):298.
[2] Dalebroux et al. (2012) ppGpp: magic beyond RNA polymerase. Nature Reviews Microbiology 10 (3):203.


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