Page last updated: 2024-10-15

guanylyl imidodiphosphate

Description

Guanylyl Imidodiphosphate: A non-hydrolyzable analog of GTP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It binds tightly to G-protein in the presence of Mg2+. The nucleotide is a potent stimulator of ADENYLYL CYCLASES. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

guanosine 5'-[beta,gamma-imido]triphosphate : A nucleoside triphosphate analogue that is GTP in which the oxygen atom bridging the beta- to the gamma- phosphate is replaced by a nitrogen atom A non-hydrolyzable analog of GTP, it binds tightly to G-protein in the presence of Mg(2+). [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID135403657
CHEMBL ID1233085
CHEBI ID78408
SCHEMBL ID2351266
SCHEMBL ID10334012
MeSH IDM0009703

Synonyms (50)

Synonym
chebi:78408 ,
CHEMBL1233085
phosphoaminophosphonic acid-guanylate ester
GNP ,
guanosine 5'-(b,g-imino)triphosphate
5'-guanylyl imidodiphosphate
gdp-np
guanosine 5'-(b,g-imido)triphosphate
guanylyl-b,g-imidodiphosphate
5'-guanylyliminodiphosphonate
5-guanylylimidodiphosphate
guanylyl-5'-(b,g-imido)diphosphate
gppnp
gppnhp
imidodiphosphoric acid, monoanhydride with 5'-guanylic acid (8ci)
5'-guanylic acid, monoanhydride with imidodiphosphoric acid (8ci,9ci)
34273-04-6
b,g-imidoguanosine-5'-triphosphate
guanylyl imidodiphosphate
phosphoaminophosphonic acid guanylate ester
1GUA
DB02082
gpp(nh)p
1RYH
gmp-pnp
guanosine 5'-[beta,gamma-imido]triphosphate
5'-guanylylimidodiphosphate
[[[[(2r,3s,4r,5r)-5-(2-amino-6-oxo-3h-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]amino]phosphonic acid
gpp(nh)p(-)
dopamine + gpp(nh)p
bdbm81791
gpp(nh)p(+)
guanosine 5'-(beta,gamma-imido)triphosphate
brimonidine gppnhp
bdbm85784
9l7gm5n7eg ,
unii-9l7gm5n7eg
5'-guanylic acid, monoanhydride with imidodiphosphoric acid
SCHEMBL2351266
gpp(nh)-p
5'-o-(hydroxy{[hydroxy(phosphonoamino)phosphoryl]oxy}phosphoryl)guanosine
SCHEMBL10334012
DTXSID20187842
5'-o-[(s)-hydroxy{[(r)-hydroxy(phosphonoamino)phosphoryl]oxy}phosphoryl]guanosine
Q4639534
[[[[(2r,3s,4r,5r)-5-(2-amino-6-oxo-1h-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]amino]phosphonic acid
PD060148
.beta.,.gamma.-imidoguanosine-5'-triphosphate
guanosine 5'-(.beta.,.gamma.-imido)triphosphate
imidodiphosphoric acid, monoanhydride with 5'-guanylic acid

Dosage Studied

ExcerptReference
" Isoproterenol dose-response curves were generated in isolated perfused hearts from sham-burned and burned guinea pigs."( Burn-induced alterations in cardiac beta-adrenergic receptors.
Horton, JW; Kaufman, TM, 1992
)
" dosing and its effects did not show tolerance on repeated dosing."( Pharmacological characterization of PD 118717, a putative piperazinyl benzopyranone dopamine autoreceptor agonist.
Christofferson, CL; Corbin, A; Demattos, S; DeWald, HA; Meltzer, LT; Myers, SL; Pugsley, TA; Shih, YH; Whetzel, SZ; Wiley, JN, 1992
)
" For each drug dose-response curves could be constituted in single hippocampal tissues at each of the time points of sacrifice."( Dose-dependent stimulation of adenylate cyclase in rat hippocampal tissue by isoprenaline, Gpp(NH)p and forskolin: lack of circadian phase-dependency.
Carlebach, R; Lemmer, B; Nitsch, R; Ohm, TG; Stiller, M, 1991
)
" However, the dose-response curves were markedly shifted to the right in the cells from diabetic rats."( Evidence for impaired coupling of receptors to Gi protein in adipocytes from streptozocin-induced diabetic rats.
Green, A; Johnson, JL, 1991
)
" We assessed the possible role of each of these components with age by measuring forskolin dose-response stimulation of adenylate cyclase activity in the presence and absence of guanosine 5'-O-(2-thiodiphosphate) (GDP-beta S) and beta,gamma-imidoguanine 5'-triphosphate (Gpp(NH)p) in myocardial membranes from F-344 rats of 3, 12, and 24 months of age."( Forskolin activation of adenylate cyclase in rat myocardium with age: effects of guanine nucleotide analogs.
Scarpace, PJ, 1990
)
" Guanine nucleotide stimulation of AC develops a biphasic dose-response curve after 3 weeks of age."( Postnatal development of striatal dopamine function. I. An examination of D1 and D2 receptors, adenylate cyclase regulation and presynaptic dopamine markers.
Bennett, JP; Broaddus, WC, 1990
)
" However, the inhibitory dose-response curves of adenylate cyclase to R-PIA, nicotinic acid, GTP, guanylylimidodiphosphate, and guanosine 5'-O-(3-thiotriphosphate) were unaltered by adrenalectomy, indicating that the inhibitory function of Gi is unimpaired by adrenalectomy."( Role of adenosine 3',5'-monophosphate and the Ri-receptor Gi-coupled adenylate cyclase inhibitory pathway in the mechanism whereby adrenalectomy increases the adenosine antilipolytic effect in rat fat cells.
de Mazancourt, P; Giot, J; Giudicelli, Y; Lacasa, D, 1989
)
" A dose-response curve for GTP gamma S indicated a concentration for half-maximal stimulation of approximately 8 microM."( GTP analogues stimulate inositol trisphosphate formation transiently in Dictyostelium.
Europe-Finner, GN; Newell, PC, 1987
)
" Maximal inhibition was observed at a concentration of 10 nM PIA, and the ED50 of the dose-response curve was 1 nM."( Adenosine inhibition of the hormonal response in the Sertoli cell is reversed by pertussis toxin.
Conti, M; DeManno, DA; Martin, MW; Monaco, L, 1988
)
" A dose of 5 mg/kg of AMPH, but not 1 mg/kg of AMPH, caused a 2-fold shift to the right in the dose-response curve for DA in stimulating AC activity when compared with saline controls."( Desensitization of rat striatal dopamine-stimulated adenylate cyclase after acute amphetamine administration.
Barnett, JV; Kuczenski, R, 1986
)
" 258, 5103-5109) but did not affect the dose-response curves for norepinephrine-induced Ca2+ mobilization and phosphorylase activation in these cells."( Studies on the hepatic alpha 1-adrenergic receptor. Modulation of guanine nucleotide effects by calcium, temperature, and age.
Blackmore, PF; Charest, R; Exton, JH; Lynch, CJ, 1985
)
" At the agonal stage, the isoproterenol dose-response curve was shifted significantly to the right in myocardial membranes from endotoxic rats, but there was no significant decrease in maximum stimulated activity."( Alterations in beta-adrenergic stimulation of myocardial adenylate cyclase in endotoxic rats.
Jones, SB; Romano, FD, 1986
)
" The dose-response relationship for EtOH stimulation of cortical AC activity in the presence of guanylylimidodiphosphate (Gpp(NH)p) was biphasic, whereas, in the striatum, a linear dose-response relationship for EtOH was found for stimulation of AC in the presence of Gpp(NH)p."( Differential effects of ethanol on the striatal and cortical adenylate cyclase system.
Hoffman, PL; Lee, JM; Luthin, GR; Saito, T; Tabakoff, B, 1987
)
" Mg2+ dose-response curves also reinforced the differences in the Ca2+/CaM requirement for Gpp(NH)p- and morphine-induced inhibition."( Ca2+/calmodulin distinguishes between guanyl-5'-yl-imidodiphosphate- and opiate-mediated inhibition of rat striatal adenylate cyclase.
Ahlijanian, MK; Cooper, DM; Halford, MK, 1987
)
" These conditions have been used to generate forskolin dose-response curves of AC activation."( Forms of adenylate cyclase, activation and/or potentiation by forskolin.
Ho, RJ; Ruiz, JA; Shi, QH, 1986
)
" Dose-response curves for GDP, GTP, and guanyl-5'-yl imidodiphosphate showed them to be equipotent."( Guanine nucleotide regulation of a mammalian myocardial muscarinic receptor system. Evidence for homo- and heterotropic cooperativity in ligand binding analyzed by computer-assisted curve fitting.
Birnbaumer, L; Entman, ML; Mattera, R; Pitts, BJ, 1985
)
" However, the dose-response curve for the GppNHp-dependent increase in [3H]forskolin binding sites is shifted to lower concentrations in the presence of prostaglandin E1."( Regulation of [3H]forskolin binding to human platelet membranes by GppNHp, NaF, and prostaglandin E1.
Nelson, CA; Seamon, KB, 1985
)
" The possibility of a decrease in enzyme sensitivity to the gonadotropin as a function of maturation ws ruled out by dose-response studies."( Developmental changes in the hormonal regulation of rat testis Sertoli cell adenylyl cyclase.
Birnbaumer, L; Means, AR; Oberwetter, JM; Van Sickle, M, 1981
)
" The dose-response curves for isoprenaline competition in binding of [125I]iodohydroxybenzylpindolol by dividing cells showed that the EC50 (effective concentration for half maximum activity) value for isoprenaline was higher in the presence of p[NH]ppG."( Characteristics of the beta-adrenergic adenylate cyclase system of developing rabbit bone-marrow erythroblasts.
Arnstein, HR; Setchenska, MS, 1983
)
" The GTP effect was not hormone-receptor mediated, since no shift was seen of the epinephrine dose-response curve toward higher sensitivity."( Essential role of GTP in epinephrine stimulation of human fat cell adenylate cyclase.
Gregerman, RI; Katz, MS; Partilla, JS; Piñeyro, MA, 1981
)
" The dose-response curves for epinephrine alone, GMP-PNP alone, or for the combination of epinephrine and GMP-PNP are similar for the newborn and adult heart preparations."( Adenylyl cyclase responsiveness to guanyl nucleotides in the developing rat heart.
Carr, L; Clark, CM; Clark, JB; Vinicor, F, 1980
)
" Dose-response curves were generated for para-aminoclonidine in the presence of vehicle alone, yohimbine (alpha-2 antagonist), idazoxan (alpha-2/I1/I2 antagonist) and prazosin (alpha-1 antagonist)."( Identification, localization and functional analysis of imidazoline and alpha adrenergic receptors in canine prostate.
Breslin, DS; Ernsberger, P; Felsen, D; Marion, DN; May, M; Nejat, RJ; Nguyen, P; Sutaria, PM; Vaughan, ED, 1994
)
" The dose-response curve of adenylate cyclase to the GTP analogue, GppNHp, was modified by 5HT, which promotes a significantly higher maximal response without altering the potency of GppNHp."( Heterologous sensitization of adenylate cyclase activity by serotonin in the rat cerebral cortex.
Brunello, N; Perez, J; Racagni, G; Rovescalli, AC; Steardo, L; Vitali, S, 1993
)
" The contractile response to carbachol was analyzed using dose-response curves."( Novel regulation of muscarinic receptors and their coupling with G proteins in smooth muscle: transient resensitization during desensitizing process.
Hishinuma, S; Kurokawa, M; Matsumoto, Y; Uchida, MK, 1993
)
" Analysis of dose-response curves for different beta-agonists revealed that (i) both the basal and the maximally stimulated activity of AC were 2-fold lower in fa/fa rats than in Fa/fa rats; (ii) BRL37344 and CGP12177 (beta 3 agonists) were less potent in fa/fa than in Fa/fa rats (Kact."( Early alterations in the brown adipose tissue adenylate cyclase system of pre-obese Zucker rat fa/fa pups: decreased G-proteins and beta 3-adrenoceptor activities.
Bazin, R; Charon, C; Diot-Dupuy, F; Emorine, LJ; Krief, S; Strosberg, AD, 1995
)
" Guanylyl imidodiphosphate (Gpp(NH)p) causes an affinity shift on the L-glutamate dose-response curve, increasing the IC50 value."( Characterization of metabotropic glutamate receptors in rat C6 glioma cells.
Albasanz, JL; Martín, M; Ros, M, 1997
)
" Dose-response curves for isoprenaline-induced force of contraction showed unchanged maximum effects but significantly increased pD2 values."( Functional coupling of overexpressed beta 1-adrenoceptors in the myocardium of transgenic mice.
Böhm, M; Flesch, M; Kilter, H; Mansier, P; Schnabel, P; Swynghedauw, B; Zolk, O, 1998
)
" Vagal ligation but not perivagal capsaicin treatment reduced the inhibitory effect of secretin on bethanechol-stimulated contraction of isolated forestomach muscle strips, causing a right shift in the dose-response curve."( Vagus nerve modulates secretin binding sites in the rat forestomach.
Chang, TM; Chey, WY; Kwon, HY; Lee, KY, 1999
)
" However, in Lewis rats amphetamine treatment increased the dose-response curve of forskolin stimulation."( Different activity of adenylyl cyclase in prefrontal cortex in three rat strains. The effect of amphetamine.
Hynie, S; Klenerová, V; Sída, P, 1998
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
nucleoside triphosphate analogue
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, ras-related C3 botulinum toxin substrate 1 isoform Rac1bHomo sapiens (human)Kd0.02760.00160.01460.0276AID977611
Chain A, ras-related C3 botulinum toxin substrate 1 isoform Rac1bHomo sapiens (human)Kd0.02760.00160.01460.0276AID977611
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (24)

Processvia Protein(s)Taxonomy
gene expressionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
dopamine secretionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
chromatin remodelingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
proteolysisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptide cross-linkingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
protein deaminationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
negative regulation of endoplasmic reticulum calcium ion concentrationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
regulation of apoptotic processProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of apoptotic processProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
apoptotic cell clearanceProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of GTPase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of cell adhesionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of neurogenesisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of small GTPase mediated signal transductionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of mitochondrial calcium ion concentrationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
bone developmentProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
branching involved in salivary gland morphogenesisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
salivary gland cavitationProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cellular response to cocaineProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cellular response to dopamineProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
positive regulation of sprouting angiogenesisProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cellular response to serotoninProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
regulation of apoptotic cell clearanceProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (10)

Processvia Protein(s)Taxonomy
protein-glutamine gamma-glutamyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
calcium ion bindingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
protein bindingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
GTP bindingProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptidase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
protein-glutamine glutaminase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
histone serotonyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
histone dopaminyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptide noradrenalinyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
peptide histaminyltransferase activityProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (12)

Processvia Protein(s)Taxonomy
collagen-containing extracellular matrixProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
nucleusProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
mitochondrionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
endoplasmic reticulumProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
cytosolProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
plasma membraneProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
focal adhesionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
extracellular matrixProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
perinuclear region of cytoplasmProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
collagen-containing extracellular matrixProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
extracellular exosomeProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
chromatinProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
nucleosomeProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
mitochondrionProtein-glutamine gamma-glutamyltransferase 2Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (8)

Assay IDTitleYearJournalArticle
AID523024Inhibition of aminoglycoside 3'-phosphotransferase 1B by PK/LDH-coupled assay2010Antimicrobial agents and chemotherapy, May, Volume: 54, Issue:5
Nucleotide selectivity of antibiotic kinases.
AID1252169Competitive inhibition of recombinant human TG2 V224 mutant deamidation activity using Cbz-Gln-Gly as substrate preincubated for 30 mins followed by substrate addition by Lineweaver-Burk plot analysis in presence of 5 mM Ca2+2015Bioorganic & medicinal chemistry letters, Nov-01, Volume: 25, Issue:21
An unprecedented dual antagonist and agonist of human Transglutaminase 2.
AID1252182Effect on closed state of recombinant human TG2 V224 mutant at 500 uM after 1 hr by native PAGE analysis in presence of 1 mM MgCl22015Bioorganic & medicinal chemistry letters, Nov-01, Volume: 25, Issue:21
An unprecedented dual antagonist and agonist of human Transglutaminase 2.
AID1252181Effect on open state of recombinant human TG2 V224 mutant at 500 uM after 1 hr by native PAGE analysis in presence of 1 mM MgCl22015Bioorganic & medicinal chemistry letters, Nov-01, Volume: 25, Issue:21
An unprecedented dual antagonist and agonist of human Transglutaminase 2.
AID523023Inhibition of APH(3')-3a by PK/LDH-coupled assay2010Antimicrobial agents and chemotherapy, May, Volume: 54, Issue:5
Nucleotide selectivity of antibiotic kinases.
AID523011Inhibition of macrolide 2'-phosphotransferase 1 by PK/LDH-coupled assay2010Antimicrobial agents and chemotherapy, May, Volume: 54, Issue:5
Nucleotide selectivity of antibiotic kinases.
AID977611Experimentally measured binding affinity data (Kd) for protein-ligand complexes derived from PDB2004The Journal of biological chemistry, Feb-06, Volume: 279, Issue:6
Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase.
AID1811Experimentally measured binding affinity data derived from PDB2004The Journal of biological chemistry, Feb-06, Volume: 279, Issue:6
Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (2,300)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901380 (60.00)18.7374
1990's759 (33.00)18.2507
2000's140 (6.09)29.6817
2010's20 (0.87)24.3611
2020's1 (0.04)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (0.04%)5.53%
Reviews28 (1.19%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other2,327 (98.77%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]