pactamycin

Summary

Summary: Antibiotic produced by Streptomyces pactum used as an antineoplastic agent. It is also used as a tool in biochemistry because it inhibits certain steps in protein synthesis.

Top Publications

  1. Kudo F, Kasama Y, Hirayama T, Eguchi T. Cloning of the pactamycin biosynthetic gene cluster and characterization of a crucial glycosyltransferase prior to a unique cyclopentane ring formation. J Antibiot (Tokyo). 2007;60:492-503 pubmed
    The biosynthetic gene (pct) cluster for an antitumor antibiotic pactamycin was identified by use of a gene for putative radical S-adenosylmethionine methyltransferase as a probe...
  2. Mankin A. Pactamycin resistance mutations in functional sites of 16 S rRNA. J Mol Biol. 1997;274:8-15 pubmed
    Mutants of an archaeon Halobacterium halobium, resistant to the universal inhibitor of translation, pactamycin, were isolated. Pactamycin resistance correlated with the presence of mutations in the 16 S rRNA gene of H...
  3. Egebjerg J, Garrett R. Binding sites of the antibiotics pactamycin and celesticetin on ribosomal RNAs. Biochimie. 1991;73:1145-9 pubmed
    The binding sites of the antibiotics pactamycin and celesticetin on the rRNAs of Escherichia coli ribosomes were investigated by a chemical footprinting procedure...
  4. Dinos G, Wilson D, Teraoka Y, Szaflarski W, Fucini P, Kalpaxis D, et al. Dissecting the ribosomal inhibition mechanisms of edeine and pactamycin: the universally conserved residues G693 and C795 regulate P-site RNA binding. Mol Cell. 2004;13:113-24 pubmed
    The crystal structures of the universal translation-initiation inhibitors edeine and pactamycin bound to ribosomal 30S subunit have revealed that edeine induces base pairing of G693:C795, residues that constitute the pactamycin binding ..
  5. Brodersen D, Clemons W, Carter A, Morgan Warren R, Wimberly B, Ramakrishnan V. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell. 2000;103:1143-54 pubmed
    ..of the 30S ribosomal subunit to determine the structures of its complexes with the antibiotics tetracycline, pactamycin, and hygromycin B...
  6. Hanessian S, Vakiti R, Chattopadhyay A, Dorich S, Lavallée C. Probing functional diversity in pactamycin toward antibiotic, antitumor, and antiprotozoal activity. Bioorg Med Chem. 2013;21:1775-86 pubmed publisher
    A total of eight new analogs of pactamycin were prepared and tested alongside pactamycin and three of its natural congeners for antibacterial, anticancer, and antiprotozoal activities...
  7. Ito T, Roongsawang N, Shirasaka N, Lu W, Flatt P, Kasanah N, et al. Deciphering pactamycin biosynthesis and engineered production of new pactamycin analogues. Chembiochem. 2009;10:2253-65 pubmed publisher
    b>Pactamycin is an aminocyclopentitol-derived natural product that has potent antibacterial and antitumor activities...
  8. Lu W, Roongsawang N, Mahmud T. Biosynthetic studies and genetic engineering of pactamycin analogs with improved selectivity toward malarial parasites. Chem Biol. 2011;18:425-31 pubmed publisher
    b>Pactamycin, one of the most densely functionalized aminocyclitol antibiotics, has pronounced antibacterial, antitumor, antiviral, and antiplasmodial activities, but its development as a clinical drug was hampered by its broad cytotoxicity...
  9. Malinowski J, Sharpe R, Johnson J. Enantioselective synthesis of pactamycin, a complex antitumor antibiotic. Science. 2013;340:180-2 pubmed publisher
    ..b>Pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties ..

More Information

Publications58

  1. Ramaiah K, Dhindsa R, Chen J, London I, Levin D. Recycling and phosphorylation of eukaryotic initiation factor 2 on 60S subunits of 80S initiation complexes and polysomes. Proc Natl Acad Sci U S A. 1992;89:12063-7 pubmed
    ..A modified model is presented with emphasis on the translocation of eIF-2 from the 40S ribosomal subunit of the 48S preinitiation complex (eIF-2.GTP.Met-tRNA(f).40S.mRNA) to the 60S subunit of the 80S initiation complex...
  2. Loreni F, Amaldi F. Translational control of terminal oligopyrimidine mRNAs requires a specific regulator. FEBS Lett. 1997;416:239-42 pubmed
    ..Our results suggest that a specific regulator is necessary to explain the translational control of these of mRNAs...
  3. Saceda M, Lindsey R, Solomon H, Angeloni S, Martin M. Estradiol regulates estrogen receptor mRNA stability. J Steroid Biochem Mol Biol. 1998;66:113-20 pubmed
    ..b>Pactamycin and puromycin, which prevent ribosome association with mRNA, inhibited the effect of estradiol on receptor mRNA ..
  4. Hofmann G, Hand S. Global arrest of translation during invertebrate quiescence. Proc Natl Acad Sci U S A. 1994;91:8492-6 pubmed
  5. Malinowski J, McCarver S, Johnson J. Diastereocontrolled construction of pactamycin's complex ureido triol functional array. Org Lett. 2012;14:2878-81 pubmed publisher
    An advanced intermediate in a projected synthesis of pactamycin has been prepared...
  6. Haussener T, Looper R. Access to the pactamycin core via an epoxide opening cascade. Org Lett. 2012;14:3632-5 pubmed publisher
    ..strategy to establish five contiguous stereocenters, in a stereocontrolled manner, on the core structure of pactamycin is described...
  7. Calcutt M, Cundliffe E. Use of a fractionated coupled transcription-translation system in the study of ribosomal resistance mechanisms in antibiotic-producing Streptomyces. J Gen Microbiol. 1989;135:1071-81 pubmed
    ..These were Streptomyces pactum and Streptomyces karnatakensis, both of which produce pactamycin. Ribosomal subunit exchange analysis further demonstrated that resistance to pactamycin in those strains is due ..
  8. Germinario R, Manuel S, Chang Z, Leckett B. Inhibitors of protein synthesis cause increased hexose transport in cultured human fibroblasts by a mechanism other than transporter translocation. J Cell Physiol. 1992;151:156-63 pubmed
    ..g., puromycin, pactamycin, or CHX) all generated hexose transport increases in a concentration-dependent fashion correlating with their ..
  9. Hatfield J, Daikh D, Adelman J, Douglass J, Bond C, Allen R. In situ hybridization detection of marked differences in pre-proopiomelanocortin messenger ribonucleic acid content of individual corticotropes and melanotropes. Endocrinology. 1989;124:1359-64 pubmed
    ..configurations was less accessable for hybridization with probes than naked mRNA, cells were preincubated with pactamycin, a potent inhibitor of ribosomal initiation of protein synthesis. Pactamycin had no effect on these results...
  10. Nagai K, Ogata K. Early effects of refeeding a complete diet on the translational initiation activity in rat liver slices. J Nutr Sci Vitaminol (Tokyo). 1989;35:279-89 pubmed
    ..subunits, where "run-off" 40S and 60S subunits had been accumulated by preincubation with 2 x 10(-6) M pactamycin, was much higher in the liver slices of refed rats than in the liver slices of fasted rats...
  11. Castrillo J, Urzainqui A, Carrasco L. The P2 and P3 regions of the poliovirus genome are preferentially translated at alkaline pH in infected HeLa cells. J Gen Virol. 1988;69 ( Pt 3):583-90 pubmed
    ..These findings suggest that truncated viral RNA is not made under these conditions. Pactamycin and sodium fluoride, two known inhibitors of the initiation of translation, blocked protein synthesis in cells ..
  12. Soares H, Galego L, Coias R, Rodrigues Pousada C. The mechanisms of tubulin messenger regulation during Tetrahymena pyriformis reciliation. J Biol Chem. 1993;268:16623-30 pubmed
    ..The effects of the inhibitors of protein synthesis, cycloheximide and pactamycin, on tubulin mRNA levels suggest that the translational apparatus plays a role in the stability of tubulin mRNA ..
  13. DeSilver D, Benedict M, Ratner D. Effects of protein synthesis inhibition on the transcription and transcript stability of Dictyostelium prespore genes. Biochim Biophys Acta. 1991;1089:309-19 pubmed
    ..The translational inhibitors cycloheximide and pactamycin stabilized existing prespore transcripts, despite their effect upon mRNA accumulation...
  14. Prostko C, Brostrom M, Brostrom C. Reversible phosphorylation of eukaryotic initiation factor 2 alpha in response to endoplasmic reticular signaling. Mol Cell Biochem. 1993;127-128:255-65 pubmed
    ..response to A23187 or DTT was not prevented by conventional inhibitors of translation including cycloheximide, pactamycin, puromycin, or verrucarin...
  15. Yamamoto K, Pellegrini M. Ribosome subunit to polysome ratios affect the synthesis of rRNA in Drosophila cells. Biochemistry. 1990;29:11029-32 pubmed
    ..decrease in the free subunit pool due to a buildup of polysomes, stimulate rRNA synthesis, whereas puromycin and pactamycin, which cause an increase in the free subunit pool, cause a decrease in rRNA synthesis...
  16. Hanessian S, Vakiti R, Dorich S, Banerjee S, Deschênes Simard B. Total synthesis of pactamycin and pactamycate: a detailed account. J Org Chem. 2012;77:9458-72 pubmed publisher
    This article describes synthetic studies that culminated in the first total synthesis of pactamycin and pactamycate and, in parallel, the two known congeners, de-6-MSA-pactamycin and de-6-MSA-pactamycate, lacking the 6-methylsalicylyl ..
  17. Mattia E, den Blaauwen J, van Renswoude J. Role of protein synthesis in the accumulation of ferritin mRNA during exposure of cells to iron. Biochem J. 1990;267:553-5 pubmed
    ..A prolonged exposure of cells to iron leads to a marked increase in ferritin mRNA levels caused by stabilization of the message. Here we show that this stabilization requires the synthesis de novo of an iron-inducible protein factor...
  18. Wilkinson M, MacLeod C. Induction of T-cell receptor-alpha and -beta mRNA in SL12 cells can occur by transcriptional and post-transcriptional mechanisms. EMBO J. 1988;7:101-9 pubmed
    ..Collectively, the data show that the accumulation of mature TCR-alpha and -beta transcripts in SL12.4 cells can be coordinately or independently induced by nuclear events involving both transcriptional and posttranscriptional mechanisms...
  19. Ratner D, Pentz W, Pelletier D. Prespore gene expression in Dictyostelium requires concomitant protein synthesis. Biochim Biophys Acta. 1989;1008:71-8 pubmed
    ..These results establish a role for protein synthesis in the transcription or transcript stability of prespore genes...
  20. Hirayama A, Eguchi T, Kudo F. A single PLP-dependent enzyme PctV catalyzes the transformation of 3-dehydroshikimate into 3-aminobenzoate in the biosynthesis of pactamycin. Chembiochem. 2013;14:1198-203 pubmed publisher
    Natural amino donation: A PLP-dependent aminotransferase PctV, encoded in the pactamycin biosynthetic gene cluster, was found to catalyze the formation of 3-aminobenzoate from 3-dehydroshikimate with L-glutamate as the amino donor...
  21. Pelczar P, Filipowicz W. The host gene for intronic U17 small nucleolar RNAs in mammals has no protein-coding potential and is a member of the 5'-terminal oligopyrimidine gene family. Mol Cell Biol. 1998;18:4509-18 pubmed
    ..Similar characteristics of the transcription start site regions in snoRNA host and ribosomal protein genes raise the possibility that expression of components of ribosome biogenesis and translational machineries is coregulated...
  22. Sharpe R, Malinowski J, Johnson J. Asymmetric synthesis of the aminocyclitol pactamycin, a universal translocation inhibitor. J Am Chem Soc. 2013;135:17990-8 pubmed publisher
    An asymmetric total synthesis of the aminocyclopentitol pactamycin is described. The title compound is delivered in 15 steps from 2,4-pentanedione...
  23. Babu S, Ramaiah K. Type 1 phosphatase inhibitors reduce the restoration of guanine nucleotide exchange activity of eukaryotic initiation factor 2B inhibited reticulocyte lysates rescued by hemin. Arch Biochem Biophys. 1996;327:201-8 pubmed
    ..The recovery of eIF-2B activity is not affected by protein synthesis inhibitors such as cycloheximide, pactamycin and puromycin, which do not affect the eIF-2alpha phosphorylation...
  24. Hua J, Hod Y. The role of protein synthesis in the decay of phosphoenolpyruvate carboxykinase messenger RNA. Mol Endocrinol. 1992;6:1418-24 pubmed
    ..incubated with cycloheximide, but not in cells incubated with other translation inhibitors, such as puromycin or pactamycin, even though protein synthesis was inhibited 85-95% by these agents...
  25. Ballesta J, Cundliffe E. Site-specific methylation of 16S rRNA caused by pct, a pactamycin resistance determinant from the producing organism, Streptomyces pactum. J Bacteriol. 1991;173:7213-8 pubmed
    Ribosomal resistance to pactamycin in clones of Streptomyces lividans containing DNA (pct) from Streptomyces pactum, the pactamycin producer, involves methylation of 16S RNA. The modified residue A-941 in S...
  26. Calcutt M, Cundliffe E. Resistance to pactamycin in clones of Streptomyces lividans containing DNA from pactamycin-producing Streptomyces pactum. Gene. 1990;93:85-9 pubmed
    A pactamycin (Pc)-resistance determinant (pct) from Streptomyces pactum has been isolated on a 4.9-kb KpnI fragment...
  27. Hirayama A, Miyanaga A, Kudo F, Eguchi T. Mechanism-Based Trapping of the Quinonoid Intermediate by Using the K276R Mutant of PLP-Dependent 3-Aminobenzoate Synthase PctV in the Biosynthesis of Pactamycin. Chembiochem. 2015;16:2484-90 pubmed publisher
    ..They also indicate that Lys276 (in the active site of PctV) plays multiple roles, including acid/base catalysis during the dehydration reaction of the quinonoid intermediate. ..
  28. Chin K, Shean C, Gottesman M. Resistance of lambda cI translation to antibiotics that inhibit translation initiation. J Bacteriol. 1993;175:7471-3 pubmed
    ..Expression of a cI-lacZ protein fusion was relatively resistant to kasugamycin and pactamycin, which inhibit translation initiation on transcripts with leaders...
  29. Herbert T, Fahraeus R, Prescott A, Lane D, Proud C. Rapid induction of apoptosis mediated by peptides that bind initiation factor eIF4E. Curr Biol. 2000;10:793-6 pubmed
    ..Thus these new data indicate that eIF4E has a direct role in controlling cell survival that is not linked to its known role in mRNA translation...
  30. Jornot L, Junod A. Differential regulation of glutathione peroxidase by selenomethionine and hyperoxia in endothelial cells. Biochem J. 1995;306 ( Pt 2):581-7 pubmed
    ..The same treatment did not result in significant changes in GP gene transcription and mRNA levels. Pactamycin, a specific inhibitor of the initiation step of translation, prevented the rise in GP activity induced by SeMet ..
  31. Ong H, Liu X, Sharma A, Hegde R, Ambudkar I. Intracellular Ca(2+) release via the ER translocon activates store-operated calcium entry. Pflugers Arch. 2007;453:797-808 pubmed
    ..In this study, we report that inhibition of the initiation step of protein synthesis (with pactamycin) resulted in detectable Ca(2+) depletion in ER and activation of SOCE...
  32. Adams E, Rinehart K. Directed biosynthesis of 5"-fluoropactamycin in Streptomyces pactum. J Antibiot (Tokyo). 1994;47:1456-65 pubmed
    A new pactamycin analogue, 5"-fluoropactamycin, was prepared by directed biosynthesis. Supplementation of the fermentation medium of Streptomyces pactum, var...
  33. Igietseme J, Herscowitz H. Immunoregulatory functions of BCG-elicited alveolar macrophages in cell-mediated immune responses. Reg Immunol. 1988;1:172-81 pubmed
    ..These results suggest that BCG-elicited AM are capable of both accessory and regulatory functions in cell-mediated immunity...
  34. Cao J, Geballe A. Ribosomal release without peptidyl tRNA hydrolysis at translation termination in a eukaryotic system. RNA. 1998;4:181-8 pubmed
    ..These results suggest that a eukaryotic cellular mechanism exists for removing stalled ribosomes from mRNAs in the absence of peptidyl tRNA hydrolysis...
  35. Davis L, Dou P, Dewit M, Kater S. Protein synthesis within neuronal growth cones. J Neurosci. 1992;12:4867-77 pubmed
    ..incorporation of 3H-leucine that was inhibited by treatment with the protein synthesis inhibitors anisomycin and pactamycin, indicating that ribosomal-dependent translation occurs in growth cones...
  36. Tourigny D, Fernández I, Kelley A, Vakiti R, Chattopadhyay A, Dorich S, et al. Crystal structure of a bioactive pactamycin analog bound to the 30S ribosomal subunit. J Mol Biol. 2013;425:3907-10 pubmed publisher
    Biosynthetically and chemically derived analogs of the antibiotic pactamycin and de-6-methylsalicylyl (MSA)-pactamycin have attracted recent interest as potential antiprotozoal and antitumor drugs. Here, we report a 3...
  37. Almabruk K, Lu W, Li Y, Abugreen M, Kelly J, Mahmud T. Mutasynthesis of fluorinated pactamycin analogues and their antimalarial activity. Org Lett. 2013;15:1678-81 pubmed publisher
    A mutasynthetic strategy has been used to generate fluorinated TM-025 and TM-026, two biosynthetically engineered pactamycin analogues produced by Streptomyces pactum ATCC 27456...
  38. Altus M, Nagamine Y. Protein synthesis inhibition stabilizes urokinase-type plasminogen activator mRNA. Studies in vivo and in cell-free decay reactions. J Biol Chem. 1991;266:21190-6 pubmed
    ..uPA mRNA became highly stable by pretreatment with either cycloheximide or pactamycin, and the stabilizing effect of cycloheximide treatment was time dependent with the full effect exerted by 60 min...
  39. Burman L, Mauro V. Analysis of rRNA processing and translation in mammalian cells using a synthetic 18S rRNA expression system. Nucleic Acids Res. 2012;40:8085-98 pubmed publisher
    ..Mutations were identified that confer resistance to pactamycin, allowing functional analysis of 40S ribosomal subunits containing synthetic 18S rRNAs by selectively blocking ..
  40. Knapp S, Yu Y. Synthesis of the oxygenated pactamycin core. Org Lett. 2007;9:1359-62 pubmed
    structure: see text]. Pactamycin, one of the most complex and densely functionalized aminocyclitol antibiotics known, presents synthetic challenges that include reactivity and sterics, relative and absolute stereochemistry, and ..
  41. Chiaberge S, Cassarino E, Mangiarotti G. The phosphorylation of protein S6 modulates the interaction of the 40 S ribosomal subunit with the 5'-untranslated region of a dictyostelium pre-spore-specific mRNA and controls its stability. J Biol Chem. 1998;273:27070-5 pubmed
    ..b>Pactamycin, but not other inhibitors of protein synthesis, prevents AC914 mRNA from being destabilized in disaggregated ..
  42. Gupta K, Ono E. Stimulation of Sendai virus C' protein synthesis by cycloheximide. Biochem J. 1997;321 ( Pt 3):811-8 pubmed
    ..was resistant to inhibitors of peptide chain elongation such as cycloheximide (CHX) and anisomycin, but not to pactamycin (an inhibitor of chain initiation) or puromycin (a peptide chain terminator)...
  43. Lopez Guerrero J, Alarcon B, Fresno M. Mechanism of recognition of herpes simplex virus type 1-infected cells by natural killer cells. J Gen Virol. 1988;69 ( Pt 11):2859-68 pubmed
    ..Blocking of HSV-1 protein synthesis or N-linked glycosylation with pactamycin or tunicamycin, respectively, prevented HSV-1-infected cells from being lysed, suggesting that HSV-1 ..
  44. Chambers S, Wang Y, Gilmore Hebert M, Kacinski B. Post-transcriptional regulation of c-fms proto-oncogene expression by dexamethasone and of CSF-1 in human breast carcinomas in vitro. Steroids. 1994;59:514-22 pubmed
    ..Furthermore, the addition of a protein synthesis inhibitor, pactamycin, to dexamethasone-treated BT20 cells results in a decrease in c-fms mRNA stability...
  45. Loertscher B, Young P, Evans P, Castle S. Diastereoselective synthesis of vicinal tertiary diols. Org Lett. 2013;15:1930-3 pubmed publisher
    ..The reaction is believed to proceed via a 1,3-chelated intermediate. One of the adducts has been transformed into a functionalized cyclopentenone resembling the core structure of pactamycin.
  46. Salati L, Ma X, McCormick C, Stapleton S, Goodridge A. Triiodothyronine stimulates and cyclic AMP inhibits transcription of the gene for malic enzyme in chick embryo hepatocytes in culture. J Biol Chem. 1991;266:4010-6 pubmed
    ..Insulin, T3, and cAMP had no effect on that pattern. In chick embryo hepatocytes in culture, factors involved in regulation of transcription by insulin, T3, and cAMP may be bound to DNA independently of hormonal treatment...
  47. Kamhi E, Yahalom G, Kass G, Hacham Y, Sperling R, Sperling J. AUG sequences are required to sustain nonsense-codon-mediated suppression of splicing. Nucleic Acids Res. 2006;34:3421-33 pubmed
    ..We further show that latent splicing can be elicited upon treatment with pactamycin-a drug known to block translation by its ability to recognize an RNA fold-but not by treatment with other drugs ..
  48. McCaffrey J, Hamilton J. Development regulation of basal and hormone-inducible phosphoenolpyruvate carboxykinase gene expression in chick embryo liver in vivo. Arch Biochem Biophys. 1994;309:10-7 pubmed
    ..and in response to dexamethasone, cAMP, retinoic acid, and the protein synthesis inhibitors, cycloheximide and pactamycin. We report here that PEPCK mRNA is constitutively expressed between 12 and 16 days of development...
  49. Pierce M, Coombs K, Young M, Avruch J. Control by insulin and insulin-related growth factor 1 of protein synthesis in a cell-free translational system from chick-embryo fibroblasts. Biochem J. 1987;244:239-42 pubmed
    ..8-3.0-fold greater rate than did controls; the increased rate persisted for 20 min in vitro. Pactamycin (0...