GTPgammaS

GTPgammaS
Names
IUPAC name
[(2S,3R,4S,5S)-5-(2-amino-6-oxo-3H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydroxyphosphinothioyl hydrogen phosphate
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
KEGG
UNII
  • InChI=34654
    Key: XOFLBQFBSOEHOG-UUOKFMHZBU
  • InChI=1/C10H16N5O13P3S/c11-10-13-7-4(8(18)14-10)12-2-15(7)9-6(17)5(16)3(26-9)1-25-29(19,20)27-30(21,22)28-31(23,24)32/h2-3,5-6,9,16-17H,1H2,(H,19,20)(H,21,22)(H2,23,24,32)(H3,11,13,14,18)/t3-,5-,6-,9-/m1/s1
  • S=P(O)(O)OP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n1cnc2c1NC(=N/C2=O)\N)[C@H](O)[C@@H]3O
Properties
C10H16N5O13P3S
Molar mass 539.24 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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GTPgammaS (GTPγS, guanosine 5'-O-[gamma-thio]triphosphate) is a non-hydrolyzable or slowly hydrolyzable G-protein-activating analog of guanosine triphosphate (GTP). Many GTP binding proteins demonstrate activity when bound to GTP, and are inactivated via the hydrolysis of the phosphoanhydride bond that links the γ-phosphate to the remainder of the nucleotide, leaving a bound guanosine diphosphate (GDP) and releasing an inorganic phosphate. This usually occurs rapidly, and the GTP-binding protein can then only be activated by exchanging the GDP for a new GTP molecule. The substitution of sulfur for one of the oxygens of the γ-phosphate of GTP creates a nucleotide that either cannot be hydrolyzed or is only slowly hydrolyzed. This prevents the GTP-binding proteins from being inactivated, and allows the cellular processes that they carry out when active to be more easily studied.

The consequences of the constitutive activation of GTP-binding proteins include stimulation of phosphoinositide hydrolysis, cyclic AMP accumulation or elimination, and activation of specific proto-oncogenes. The 35S labelled radioligand of the compound, 35SGTPγS, is used in autoradiography and G-protein binding studies.

References

  1. ↑ Harrison C, Traynor JR (December 12, 2003). "The [35S]GTPγS binding assay: approaches and applications in pharmacology". Life Sciences. 74 (4): 489–508. doi:10.1016/j.lfs.2003.07.005. PMID 14609727. Retrieved April 26, 2021.
  2. ↑ Spoerner M, Nuehs A, Herrmann C, Steiner G, Kalbitzer HR (March 2007). "Slow conformational dynamics of the guanine nucleotide-binding protein Ras complexed with the GTP analogue GTPγS". The FEBS Journal. 274 (6): 1419–1433. doi:10.1111/j.1742-4658.2007.05681.x. PMID 17302736.
  3. ↑ White HL, Scates PW (1991). "Effects of GTPγS and other nucleotides on phosphoinositide metabolism in crude rat brain synaptosomal preparations". Neurochemistry International. 18 (3): 381–387. doi:10.1016/0197-0186(91)90170-I. PMID 20504715. S2CID 44683770. Retrieved April 26, 2021.
  4. ↑ Baker SP, Scammells PJ, Belardinelli L (July 2000). "Differential A1-adenosine receptor reserve for inhibition of cyclic AMP accumulation and G-protein activation in DDT1 MF-2 cells". British Journal of Pharmacology. 130 (5): 1156–1164. doi:10.1038/sj.bjp.0703405. PMC 1572163. PMID 10882402.
  5. ↑ Pennington SR, Hesketh TR, Metcalfe JC (January 25, 1988). "GTPγS activation of proto-oncogene expression in transiently permeabilised Swiss 3T3 fibroblasts". FEBS Letters. 227 (2): 203–208. Bibcode:1988FEBSL.227..203P. doi:10.1016/0014-5793(88)80899-8. PMID 3276558.
  6. ↑ Strange PG (November 2010). "Use of the GTPγS ([35S]GTPγS and Eu-GTPγS) binding assay for analysis of ligand potency and efficacy at G protein-coupled receptors". British Journal of Pharmacology. 161 (6): 1238–1249. doi:10.1111/j.1476-5381.2010.00963.x. PMC 3000650. PMID 20662841.