diphosphates

Summary

Summary: Inorganic salts of phosphoric acid that contain two phosphate groups.

Top Publications

  1. Malinen A, Turtola M, Parthiban M, Vainonen L, Johnson M, Belogurov G. Active site opening and closure control translocation of multisubunit RNA polymerase. Nucleic Acids Res. 2012;40:7442-51 pubmed publisher
    ..The RNAP translocation mechanism is exploited by the antibiotic tagetitoxin, which mimics pyrophosphate and induces backward translocation by closing the active site...
  2. Patterson D, Zweifel M, Middleton M, Price P, Folkes L, Stratford M, et al. Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors. Clin Cancer Res. 2012;18:1415-25 pubmed publisher
    ..Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents...
  3. Pace D, Fang J, Cintron R, Docampo M, Moreno S. Overexpression of a cytosolic pyrophosphatase (TgPPase) reveals a regulatory role of PP(i) in glycolysis for Toxoplasma gondii. Biochem J. 2011;440:229-40 pubmed publisher
    ..These results implicate PP(i) as having a significant regulatory role in glycolysis and, potentially, other downstream processes that regulate growth and cell division...
  4. Eberl M, Moser B. Monocytes and gammadelta T cells: close encounters in microbial infection. Trends Immunol. 2009;30:562-8 pubmed publisher
    ..Vgamma9/Vdelta2 T cells act thus as a cellular switch between innate and adaptive defence mechanisms...
  5. Da L, Wang D, Huang X. Dynamics of pyrophosphate ion release and its coupled trigger loop motion from closed to open state in RNA polymerase II. J Am Chem Soc. 2012;134:2399-406 pubmed publisher
    ..Our simulations provide predictions to guide future experimental tests...
  6. Kamiya H, Hori M, Arimori T, Sekiguchi M, Yamagata Y, Harashima H. NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity. DNA Repair (Amst). 2009;8:1250-4 pubmed publisher
    ..These results suggest that the NUDT5 protein eliminates various oxidized deoxyribonucleoside diphosphates from the nucleotide pool and prevents their toxic effects.
  7. Prosdocimo D, Wyler S, ROMANI A, O Neill W, Dubyak G. Regulation of vascular smooth muscle cell calcification by extracellular pyrophosphate homeostasis: synergistic modulation by cyclic AMP and hyperphosphatemia. Am J Physiol Cell Physiol. 2010;298:C702-13 pubmed publisher
    ..These observations support a model in which extracellular PP(i) generation mediated by both ANK- and ATP release-dependent mechanisms serves as a critical regulator of VSMC calcification...
  8. Wang H, Fang Z, Morita C. Vgamma2Vdelta2 T Cell Receptor recognition of prenyl pyrophosphates is dependent on all CDRs. J Immunol. 2010;184:6209-22 pubmed publisher
    ..This underscores its parallels to innate immune receptors. Our results also provide strong evidence for the existence of an Ag-presenting molecule for prenyl pyrophosphates...
  9. Dalal S, Burchill S. Preclinical evaluation of vascular-disrupting agents in Ewing's sarcoma family of tumours. Eur J Cancer. 2009;45:713-22 pubmed publisher
    ..001). This study demonstrates that OXi4503/CA1P is a potent VDA in ESFT and in combination with conventional cytotoxic agents represents a promising treatment strategy for this tumour group...

More Information

Publications62

  1. Tsai M, Shimizu H, Sohma Y, Li M, Hwang T. State-dependent modulation of CFTR gating by pyrophosphate. J Gen Physiol. 2009;133:405-19 pubmed publisher
    ..Finally, we show that MgAMP-PNP exerts its effects on CFTR gating via a similar mechanism as MgPPi. The structural and functional significance of our findings is discussed...
  2. O Neill W, Sigrist M, McIntyre C. Plasma pyrophosphate and vascular calcification in chronic kidney disease. Nephrol Dial Transplant. 2010;25:187-91 pubmed publisher
    ..We sought to determine whether plasma PPi is affected by dialysis or the mode of dialysis and whether it correlates with vascular calcification...
  3. Bennouna J, Levy V, Sicard H, Senellart H, Audrain M, Hiret S, et al. Phase I study of bromohydrin pyrophosphate (BrHPP, IPH 1101), a Vgamma9Vdelta2 T lymphocyte agonist in patients with solid tumors. Cancer Immunol Immunother. 2010;59:1521-30 pubmed publisher
    ..The present phase I trial was conducted with the aim of determining the maximum-tolerated dose (MTD) and safety of IPH1101 combined with a low dose of IL-2 in patients with solid tumors...
  4. Yadav M, Simão A, Narisawa S, Huesa C, McKee M, Farquharson C, et al. Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: a unified model of the mechanisms of initiation of skeletal calcification. J Bone Miner Res. 2011;26:286-97 pubmed publisher
  5. Rice L, Pampo C, Lepler S, Rojiani A, Siemann D. Support of a free radical mechanism for enhanced antitumor efficacy of the microtubule disruptor OXi4503. Microvasc Res. 2011;81:44-51 pubmed publisher
    ..These findings indicate that while the predominant in vivo effect of OXi4503 is clearly due to microtubule collapse and vascular shut-down, the formation of toxic free radicals likely contributes to its enhanced potency...
  6. Rodrigues T, Foster B, Silvério K, Martins L, Casati M, Sallum E, et al. Correction of hypophosphatasia-associated mineralization deficiencies in vitro by phosphate/pyrophosphate modulation in periodontal ligament cells. J Periodontol. 2012;83:653-63 pubmed publisher
  7. Jiang J, Lazarus M, Pasquina L, Sliz P, Walker S. A neutral diphosphate mimic crosslinks the active site of human O-GlcNAc transferase. Nat Chem Biol. 2011;8:72-7 pubmed publisher
    ..Though this unprecedented double-displacement mechanism reflects the unique architecture of the OGT active site, related dicarbamate scaffolds may inhibit other enzymes that bind nucleotide-containing substrates...
  8. Yi Y, Sutovsky M, Kennedy C, Sutovsky P. Identification of the inorganic pyrophosphate metabolizing, ATP substituting pathway in mammalian spermatozoa. PLoS ONE. 2012;7:e34524 pubmed publisher
  9. Cabillic F, Toutirais O, Lavoue V, De la Pintiere C, Daniel P, Rioux Leclerc N, et al. Aminobisphosphonate-pretreated dendritic cells trigger successful Vgamma9Vdelta2 T cell amplification for immunotherapy in advanced cancer patients. Cancer Immunol Immunother. 2010;59:1611-9 pubmed publisher
    ..Thus, this method of generating Vgamma9Vdelta2 T cells leads eligible for Vgamma9Vdelta2 T cell adoptive immunotherapy the HCC and mCRC patients...
  10. Meng Y, Ingram Smith C, Cooper L, Smith K. Characterization of an archaeal medium-chain acyl coenzyme A synthetase from Methanosarcina acetivorans. J Bacteriol. 2010;192:5982-90 pubmed publisher
    ..Characterization of the enzyme variants indicates that these six residues are critical in acyl substrate binding and catalysis, and even conservative alterations significantly reduced the catalytic ability of the enzyme...
  11. Murshed M, McKee M. Molecular determinants of extracellular matrix mineralization in bone and blood vessels. Curr Opin Nephrol Hypertens. 2010;19:359-65 pubmed publisher
    ..Here we review new findings on direct molecular determinants of mineralization operating locally at the level of the extracellular matrix, with a focus on bone and blood vessels...
  12. Brown A, Eberl M, Crick D, Jomaa H, Parish T. The nonmevalonate pathway of isoprenoid biosynthesis in Mycobacterium tuberculosis is essential and transcriptionally regulated by Dxs. J Bacteriol. 2010;192:2424-33 pubmed publisher
    ..Increased expression of this operon was seen in cells overexpressing Dxs1, indicating that transcriptional control is effected by the first enzyme of the pathway via an unknown regulator...
  13. Golosov A, Warren J, Beese L, Karplus M. The mechanism of the translocation step in DNA replication by DNA polymerase I: a computer simulation analysis. Structure. 2010;18:83-93 pubmed publisher
    ..These roles are consistent with the high level of conservation of Y714 and the two glycine residues at these positions. It is likely that a corresponding mechanism is applicable to other polymerases...
  14. O Neill W, Lomashvili K, Malluche H, Faugere M, Riser B. Treatment with pyrophosphate inhibits uremic vascular calcification. Kidney Int. 2011;79:512-7 pubmed publisher
    ..Thus, exogenous pyrophosphate can inhibit uremic vascular calcification without producing adverse effects on bone...
  15. Ciancaglini P, Yadav M, Simão A, Narisawa S, Pizauro J, Farquharson C, et al. Kinetic analysis of substrate utilization by native and TNAP-, NPP1-, or PHOSPHO1-deficient matrix vesicles. J Bone Miner Res. 2010;25:716-23 pubmed publisher
    ..NPP1 does not have a major role in PP(i) generation from ATP at the level of MVs, in contrast to its accepted role on the surface of the osteoblasts and chondrocytes, but rather acts as a phosphatase in the absence of TNAP...
  16. Russell R. Bisphosphonates: the first 40 years. Bone. 2011;49:2-19 pubmed publisher
    ..The adventure that began in Davos more than 40 years ago is not yet over...
  17. Eberl M, Roberts G, Meuter S, Williams J, Topley N, Moser B. A rapid crosstalk of human gammadelta T cells and monocytes drives the acute inflammation in bacterial infections. PLoS Pathog. 2009;5:e1000308 pubmed publisher
  18. Wankhede M, Dedeugd C, Siemann D, Sorg B. In vivo functional differences in microvascular response of 4T1 and Caki-1 tumors after treatment with OXi4503. Oncol Rep. 2010;23:685-92 pubmed
    ..The differential responses of these two tumor-types suggest that further investigation of the mechanisms of action of VDAs and individual characterization of tumor VDA-responses may be needed for optimal clinical use of these agents...
  19. Ali Z, Shao L, Halliday L, Reichenberg A, Hintz M, Jomaa H, et al. Prolonged (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vgamma2Vdelta2 T cells in macaques. J Immunol. 2007;179:8287-96 pubmed
    ..Thus, the prolonged HMBPP-driven antimicrobial and cytotoxic responses of pulmonary and systemic Vgamma2Vdelta2 T cells may confer immunotherapeutics against infectious diseases and cancers...
  20. Van den Bos T, Handoko G, Niehof A, Ryan L, Coburn S, Whyte M, et al. Cementum and dentin in hypophosphatasia. J Dent Res. 2005;84:1021-5 pubmed
    ..Our findings suggest that mineralization of dentin is less likely to be under the influence of the inhibitory action of pyrophosphate than mineralization of cementum...
  21. Morita C, Jin C, Sarikonda G, Wang H. Nonpeptide antigens, presentation mechanisms, and immunological memory of human Vgamma2Vdelta2 T cells: discriminating friend from foe through the recognition of prenyl pyrophosphate antigens. Immunol Rev. 2007;215:59-76 pubmed
    ..Thus, primary infections with HMBPP-producing bacteria are perceived by Vgamma2Vdelta2 T cells as a repeat infection. Extensive efforts are underway to harness these cells to treat a variety of cancers and to provide microbial immunity...
  22. Zaka R, Williams C. Role of the progressive ankylosis gene in cartilage mineralization. Curr Opin Rheumatol. 2006;18:181-6 pubmed
    ..The purpose of this review is to highlight recent work on the role of ANK in physiological and pathological calcification of articular and growth plate cartilage...
  23. Hirose J, Ryan L, Masuda I. Up-regulated expression of cartilage intermediate-layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease. Arthritis Rheum. 2002;46:3218-29 pubmed
  24. Johnson R, Strausbauch M, Cooper R, Register J. Rapid kinetic analysis of transcription elongation by Escherichia coli RNA polymerase. J Mol Biol. 2008;381:1106-13 pubmed publisher
    ..Rapid release of pyrophosphate from the elongation complex at a rate consistent with productive transcription elongation occurs only in the presence of the correct next nucleotide for incorporation into the transcript...
  25. Smith A, Meyer P, Asthana D, Ashman M, Scott W. Intracellular substrates for the primer-unblocking reaction by human immunodeficiency virus type 1 reverse transcriptase: detection and quantitation in extracts from quiescent- and activated-lymphocyte subpopulations. Antimicrob Agents Chemother. 2005;49:1761-9 pubmed
    ..While PP(i)-dependent excision may contribute to AZT resistance in vivo, it is likely that selection of AZT-resistant mutants occurs primarily in an environment where the ATP-dependent reaction predominates...
  26. Vermijlen D, Ellis P, Langford C, Klein A, Engel R, Willimann K, et al. Distinct cytokine-driven responses of activated blood gammadelta T cells: insights into unconventional T cell pleiotropy. J Immunol. 2007;178:4304-14 pubmed
  27. Farré E, Tech S, Trethewey R, Fernie A, Willmitzer L. Subcellular pyrophosphate metabolism in developing tubers of potato (Solanum tuberosum). Plant Mol Biol. 2006;62:165-79 pubmed
    ..These results are discussed both with respect to our previous hypotheses and to current models of the compartmentation of potato tuber metabolism...
  28. Andreasson H, Nilsson M, Budowle B, Frisk S, Allen M. Quantification of mtDNA mixtures in forensic evidence material using pyrosequencing. Int J Legal Med. 2006;120:383-90 pubmed
    ..This mtDNA quantification assay is an easy to use, fast and accurate quantification system, with the ability to resolve and interpret major and minor mtDNA components in forensic mixture samples...
  29. Elahi E, Ronaghi M. Pyrosequencing: a tool for DNA sequencing analysis. Methods Mol Biol. 2004;255:211-9 pubmed
  30. Sheng Y, Hua J, Pinney K, Garner C, Kane R, Prezioso J, et al. Combretastatin family member OXI4503 induces tumor vascular collapse through the induction of endothelial apoptosis. Int J Cancer. 2004;111:604-10 pubmed
    ..The time course of the tumor vascular response observed with OXI4503 treatment supports this drug for development as a stand alone therapy, and also lends support for the use of the drug in combination with other cancer therapies...
  31. Reichenberg A, Hintz M, Kletschek Y, Kuhl T, Haug C, Engel R, et al. Replacing the pyrophosphate group of HMB-PP by a diphosphonate function abrogates Its potential to activate human gammadelta T cells but does not lead to competitive antagonism. Bioorg Med Chem Lett. 2003;13:1257-60 pubmed
    ..However, replacing the pyrophosphate by a P-CH(2)-P function abrogates the bioactivity drastically, with HMB-PCP having a EC(50) of only 5.3 microM...
  32. Wang W, Xu J, Du B, Kirsch T. Role of the progressive ankylosis gene (ank) in cartilage mineralization. Mol Cell Biol. 2005;25:312-23 pubmed
  33. Nociti F, Berry J, Foster B, Gurley K, Kingsley D, Takata T, et al. Cementum: a phosphate-sensitive tissue. J Dent Res. 2002;81:817-21 pubmed
    ..This information may prove valuable in attempts to design successful therapies for regenerating periodontal tissues...
  34. Suk E, Malkin I, Dahm S, Kalichman L, Ruf N, Kobyliansky E, et al. Association of ENPP1 gene polymorphisms with hand osteoarthritis in a Chuvasha population. Arthritis Res Ther. 2005;7:R1082-90 pubmed
    ..Thus, our data highlights variability of ENPP1 as an important genetic factor in the pathogenesis of idiopathic osteoarthritis...
  35. Schmidt A, Gershenzon J. Cloning and characterization of two different types of geranyl diphosphate synthases from Norway spruce (Picea abies). Phytochemistry. 2008;69:49-57 pubmed
    ..and one encoded by a similar gene sequence from Quercus robur gave substantial amounts of the larger prenyl diphosphates, FPP and GGPP, in addition to GPP...
  36. Doostzadeh J, Shokralla S, Absalan F, Jalili R, Mohandessi S, Langston J, et al. High throughput automated allele frequency estimation by pyrosequencing. PLoS ONE. 2008;3:e2693 pubmed publisher
    ..We also discuss potential improvements of the software for more accurate allele frequency analysis...
  37. Boëdec A, Sicard H, Dessolin J, Herbette G, Ingoure S, Raymond C, et al. Synthesis and biological activity of phosphonate analogues and geometric isomers of the highly potent phosphoantigen (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate. J Med Chem. 2008;51:1747-54 pubmed publisher
    ..These results indicate that the use of bioisosteric analogues of HDMAPP may represent promising new leads for immunotherapy...
  38. Devilder M, Maillet S, Bouyge Moreau I, Donnadieu E, Bonneville M, Scotet E. Potentiation of antigen-stimulated V gamma 9V delta 2 T cell cytokine production by immature dendritic cells (DC) and reciprocal effect on DC maturation. J Immunol. 2006;176:1386-93 pubmed
  39. Malcontenti Wilson C, Chan L, Nikfarjam M, Muralidharan V, Christophi C. Vascular targeting agent Oxi4503 inhibits tumor growth in a colorectal liver metastases model. J Gastroenterol Hepatol. 2008;23:e96-e104 pubmed
    ..Despite evidence of its efficacy in certain malignancies, the effect on colorectal liver metastases remains largely unknown. This study investigates the effect of Oxi4503 on colorectal liver metastases in a murine model...
  40. Chan L, Malcontenti Wilson C, Muralidharan V, Christophi C. Effect of vascular targeting agent Oxi4503 on tumor cell kinetics in a mouse model of colorectal liver metastasis. Anticancer Res. 2007;27:2317-23 pubmed
    ..This agent appears to selectively target the endothelial cytoskeleton with resultant vessel occlusion and tumor necrosis...
  41. Rojas R, Torres M, Fournie J, Harding C, Boom W. Phosphoantigen presentation by macrophages to mycobacterium tuberculosis--reactive Vgamma9Vdelta2+ T cells: modulation by chloroquine. Infect Immun. 2002;70:4019-27 pubmed
    ..Chloroquine, by inhibiting membrane traffic, may increase association and retention of phosphoantigens with cell surface membrane molecules on macrophages...
  42. Eberl M, Hintz M, Jamba Z, Beck E, Jomaa H, Christiansen G. Mycoplasma penetrans is capable of activating V gamma 9/V delta 2 T cells while other human pathogenic mycoplasmas fail to do so. Infect Immun. 2004;72:4881-3 pubmed
    ..Consequently, this pathogen is capable of stimulating human V gamma 9/V delta 2 T cells...
  43. Chan L, Malcontenti Wilson C, Muralidharan V, Christophi C. Alterations in vascular architecture and permeability following OXi4503 treatment. Anticancer Drugs. 2008;19:17-22 pubmed
    ..A combination of OXi4503 with other chemotherapeutic modalities might achieve complete tumor eradication and improve long-term survival...
  44. Burjanadzé M, Condomines M, Reme T, Quittet P, Latry P, Lugagne C, et al. In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma. Br J Haematol. 2007;139:206-16 pubmed
    ..This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells...
  45. Arnold J, Cameron C. Poliovirus RNA-dependent RNA polymerase (3Dpol): pre-steady-state kinetic analysis of ribonucleotide incorporation in the presence of Mg2+. Biochemistry. 2004;43:5126-37 pubmed
    ..We discuss the implications of this work on the development of RNA-dependent RNA polymerase inhibitors for use as antiviral agents...
  46. Liu Q, Sommer S. PAP: detection of ultra rare mutations depends on P* oligonucleotides: "sleeping beauties" awakened by the kiss of pyrophosphorolysis. Hum Mutat. 2004;23:426-36 pubmed
    ..Thus, PAP also can form the basis of microarray-based scanning or resequencing methods to detect virtually all mutations...
  47. Ismaili J, Olislagers V, Poupot R, Fournie J, Goldman M. Human gamma delta T cells induce dendritic cell maturation. Clin Immunol. 2002;103:296-302 pubmed
    ..We conclude that gamma delta T cell activation might result in DC maturation and thereby in enhanced alpha beta T cell responses...
  48. Harmey D, Hessle L, Narisawa S, Johnson K, Terkeltaub R, Millan J. Concerted regulation of inorganic pyrophosphate and osteopontin by akp2, enpp1, and ank: an integrated model of the pathogenesis of mineralization disorders. Am J Pathol. 2004;164:1199-209 pubmed
    ..The hypomineralization observed in Akp2(-/-) mice arises from the combined inhibitory effects of PP(i) and OPN. In contrast, NPP1 or ANK deficiencies cause a decrease in the PP(i) and OPN pools that leads to hypermineralization...
  49. Zhou G, Shirakura H, Kamahori M, Okano K, Nagai K, Kambara H. A gel-free SNP genotyping method: bioluminometric assay coupled with modified primer extension reactions (BAMPER) directly from double-stranded PCR products. Hum Mutat. 2004;24:155-63 pubmed
    ..As all reactions can be carried out in a single tube, the method will be useful for realizing a fully automated genotyping system...
  50. Zhang Y, Johnson K, Russell R, Wordsworth B, Carr A, Terkeltaub R, et al. Association of sporadic chondrocalcinosis with a -4-basepair G-to-A transition in the 5'-untranslated region of ANKH that promotes enhanced expression of ANKH protein and excess generation of extracellular inorganic pyrophosphate. Arthritis Rheum. 2005;52:1110-7 pubmed
    ..This study investigated the potential for ANKH sequence variants to promote sporadic chondrocalcinosis...
  51. Murshed M, Harmey D, Millan J, McKee M, Karsenty G. Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev. 2005;19:1093-104 pubmed
  52. Scott Ward T, Cai Z, Dawson E, Doherty A, da Paula A, Davidson H, et al. Chimeric constructs endow the human CFTR Cl- channel with the gating behavior of murine CFTR. Proc Natl Acad Sci U S A. 2007;104:16365-70 pubmed
    ..We conclude that the NBDs of murine CFTR determine the unique gating behavior of its subconductance state, whereas NBD2 controls channel potentiation by PP(i)...
  53. Johnson K, Terkeltaub R. Upregulated ank expression in osteoarthritis can promote both chondrocyte MMP-13 expression and calcification via chondrocyte extracellular PPi excess. Osteoarthritis Cartilage. 2004;12:321-35 pubmed
    ..Therefore, we assessed if dysregulated wild-type ANK expression could contribute to pathogenesis of idiopathic degenerative arthropathy through elevated ecPP(i)...