Applied Microbiology and Biotechnology

, Volume 69, Issue 3, pp 237–244 | Cite as

Thiosugars: new perspectives regarding availability and potential biochemical and medicinal applications

Mini-Review

Abstract

Thiosugars, containing a sulfur atom as heteroatom or a disaccharide linked via a sulfur bridge, possess unique physicochemical properties such as water solubility, which differs from conventional functionalized monosaccharides. The differences in biological activities between thiosugars and their oxygen analogs depend on geometric, conformational, and flexibility differences. They depend also on their electronic differences, the sulfide function being less electronegative and more polarizable than the ethereal moiety. Many functionalized thiosugars occur naturally and are potential targets for the development of carbohydrate-based therapeutics. Among the few new examples of the potential new targets are salacinol and kotalanol, tagetitoxin, thiolactomycin and analogues, mycothiol and analogues, and S-nitrosothiols. These new developments and representative examples of functionalized thiosugar prototypes as potential new targets are presented in this mini review.

References

  1. Bornemann C, Jardine MA, Spies HSC, Steenkamp DJ (1997) Biosynthesis of mycothiol: elucidation of the sequence of steps in Mycobacterium smegmatis. Biochem J 325:623–629PubMedGoogle Scholar
  2. Bouchet F, Driguez H, McAuliffe JC, Stick RV, Tilbrook DMG, Williams SJ (1996) A new approach to some 1,6-dideoxy-1,6-epithiosugars. Aust J Chem 49:343–348CrossRefGoogle Scholar
  3. Buchmeier NA, Newton GL, Koledin T, Fahey RC (2003) Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibiotics. Mol Microbiol 47:1723–1732CrossRefPubMedGoogle Scholar
  4. Capon RJ, MacLeod JK (1987) 5-Thio-d-mannose from marine sponge Clathria pyramida (Lendenfeld). The first example of a naturally occurring 5-thiosugar. J Chem Soc Chem Commun 15:1200–1201CrossRefGoogle Scholar
  5. Chambers MS, Thomas EJ (1989) Total synthesis of (5S)-thiolactomycin-revision of the absolute configuration of the natural products. J Chem Soc Chem Commun 23–24Google Scholar
  6. Davis BG, Ward SJ, Rendle PM (2001) Glycosyldisulfides: a new class of solution and solid phase glycosyl donors. Chem Commun 189–190Google Scholar
  7. Defaye J, Gelas J (1991) Thio-oligosaccharides: their synthesis and reactions with enzymes. In: Atta-ur-Rahman (ed) Studies in natural products chemistry, vol 8E. Elsevier, Amsterdam, pp 315–357Google Scholar
  8. Dent BR, Furneaux RH, Gainsford GJ, Lynch GP (1999) Synthesis studies of structural analogues of tagetitoxin: 4-O-acetyl-3-amino-1,6-anhydro-3-deoxy-d-gulose 2-phosphate. Tetrahedron 55:6977–6996CrossRefGoogle Scholar
  9. Dey PM, Witczak ZJ (2003) Functionalized S-thio-di and S-oligosaccharide precursors as templates for novel SLex/a mimetic antimetastatic agents. Mini Rev Med Chem 3:271–280CrossRefPubMedGoogle Scholar
  10. Diez D, Beneitez MT, Marcos IS, Garrido NM, Basabe P, Urones JG (2004) 1-Hydroxymethyl-4-phenylsulfonylbutadiene, a versatile building block for the synthesis of 2,3,4-trisubstituted terahydrothiophenes. Molecules 9:323–329CrossRefGoogle Scholar
  11. Douglas JD, Senior SJ, Morehouse C, Phetsukiri B, Campbell IB, Besra GS, Minnikin DE (2002) Analogues of thiolactomycin: potential drugs with enhanced anti-microbial activity. Microbiology 148:3101–3109PubMedGoogle Scholar
  12. Driguez H (1997) Thiooligosaccharides in glycobiology. Top Curr Chem 187:85–116Google Scholar
  13. Eisele T, Toepfer A, Kretzschmar G, Schmidt RR (1996) Synthesis of S-thiolinked analogue of sialyl Lewis X. Tetrahedron Lett 37:1389–1392CrossRefGoogle Scholar
  14. Fahey JW, Zalcmann AT, Talalay P (2001) The chemical diversity and distribution of glucosinolates and isocyanates among plants. Phytochemistry 56:5–51CrossRefPubMedGoogle Scholar
  15. Fang FC (1997) Mechanism of nitric oxide-related antimicrobial activity. J Clin Invest 99:2818–2825PubMedCrossRefGoogle Scholar
  16. Fernandez-Bolanos JG, Al-Masoudi AL, Maya I (2001) Sugar derivatives having sulfur in the ring. Adv Carbohydr Chem Biochem 57:21–98PubMedGoogle Scholar
  17. Ghavami A, Sadalapure KS, Johnston BD, Lobera M, Snider BB, Pinto BM (2003) Improved syntheses of naturally occurring glycosidase inhibitor salacinol. Synlett 1259–1262Google Scholar
  18. Ibatullin FM, Shabalin KA, Janis JV, Selivanov SI (2001) Stereoselective synthesis of thioxylooligosaccharides from S-glycosyl iso-thiourea precursors. Tetrahedron Lett 42:565–4567CrossRefGoogle Scholar
  19. Ibatullin FM, Shabalin KA, Janis JV, Shavva AG (2003) Reaction of 1,2-trans-glycosyl acetates with thiourea: a new entry to 1-thiosugars. Tetrahedron Lett 44:7961–7964CrossRefGoogle Scholar
  20. Ioannou M, Porter MJ, Saez F (2002) A ring expansion reaction of 1,3-oxathiolanes. Chem Commun 346–347Google Scholar
  21. Izquierdo I, Plaza MT, Asenjo R, Ramirez A (2002) Thioanhydrosugars. Part 9. Enantiospecific synthesis of a polyhydroxythiolane, key intermediate for the preparation of glycosidase inhibitors bearing inner thiosulfonium salt. Tetrahedron Asymmetry 13:1417–1421CrossRefGoogle Scholar
  22. Jahn M, Withers SG (2003) New approaches to enzymatic oligosaccharide synthesis: glycosynthases and thioglycoligases. Biocatal Biotransform 21(4/5):159–166CrossRefGoogle Scholar
  23. Jahn M, Marles J, Warren RAJ, Withers SG (2003) Thioglycoligases: mutant glycosidases for thioglycoside synthesis. Angew Chem 115(3):366–368CrossRefGoogle Scholar
  24. Jardine MA, Spies HSC, Nkambule CM, Gammon DW, Steenkamp DJ (2002) Synthesis of mycothiol, 1d-1-O-(2-[N-acetyl-l-cysteinyl]amino-2-deoxy-α-d-gluco-pyranosyl)-myo-inositol, principal low molecular mass thiol in the actinomycetes. Bioorg Med Chem 10:875–881CrossRefPubMedGoogle Scholar
  25. Jones AL, Herbert D, Rutter AJ, Dancer JE, Harwood JL (2000) Novel inhibitors of the condensing enzymes of the type II fatty acid synthase of pea (Pisum sativum). Biochem J 347:205–209CrossRefPubMedGoogle Scholar
  26. Jones SM, Urch JE, Brun R, Harwood JL, Berry C, Gilbert IH (2004) Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents. Bioorg Med Chem 12:683–692CrossRefPubMedGoogle Scholar
  27. Khan F, Pearson RJ, Newton DJ, Belch JJ, Butler AR (2003) Chemical synthesis and microvascular effects of new nitric oxide donors in humans. Clin Sci 105:577–584CrossRefPubMedGoogle Scholar
  28. Knapp S, Gonzalez S, Myers DS, Eckman LL, Bewley CA (2002) Shortcut to mycothiol analogues. Org Lett 4:4337–4339CrossRefPubMedGoogle Scholar
  29. Knapp S, Amorelli B, Darout E, Ventocilla CC, Goldman LM, Huhn RA, Minihan EC (2005) A family of mycothiol analogues. J Carbohydr Chem 24:103–130CrossRefGoogle Scholar
  30. Kremer L, Douglas JD, Baulard AR, Morehouse C, Guy MR, Alland D, Dover LG, Lakey JH, Jacobs WR Jr, Brennan PJ, Minnikin DE, Besra GS (2000) Thiolactomycin and related analogues as novel anti-mycobacterial agents targeting KasA and KasB condensing enzymes in Mycobacterium tuberculosis. J Biol Chem 275:16857–16864CrossRefPubMedGoogle Scholar
  31. Lee S, Rosazza JPN (2004) First total synthesis of mycothiol and mycothiol disulfide. Org Lett 6:365–368CrossRefPubMedGoogle Scholar
  32. Liu H, Pinto BM (2005) Efficient synthesis of glucosidase inhibitor, blintol the selenium analogue of the naturally occurring glucosidase inhibitor salacinol. J Org Chem 70:735–755CrossRefPubMedGoogle Scholar
  33. Lundt I, Skelbaek-Pedersen B (1981) Ethylation of thiolaevoglucosan to a crystalline sulfonium salt and reaction of the latter with nucleophile. Acta Chem Scand B 35:637–642Google Scholar
  34. Mathews DE, Durbin RD (1990) Tagetitoxin inhibits RNA synthesis directed by RNA polymerases from chloroplasts and Escherichia coli. J Biol Chem 265:493–498PubMedGoogle Scholar
  35. Matsuda H, Morikawa T, Yoshikawa M (2002) Antidiabetogenic constituents from several natural medicines. Pure Appl Chem 74:1301–1308CrossRefGoogle Scholar
  36. Mavratzotis M, Dourtoglou V, Lorin C, Rollin P (1996) Glucosinolate chemistry. First synthesis of glucosinolates bearing an external thiofunction. Tetrahedron Lett 37:5699–5700CrossRefGoogle Scholar
  37. Maynes JT, Garen C, Cherney MM, Newton G, Arad D, Av-Gay Y, Fahey RC, James MNG (2003) The crystal structure of 1-d-myo-inosityl-2-acetamido-2-deoxy-α-d-glucopyranoside deacetylase (MshB) from Mycobacterium tuberculosis reveals a zinc hydrolase with lactate dehydrogenase fold. J Biol Chem 278:47166–47170CrossRefPubMedGoogle Scholar
  38. McFadden JM, Frehywot GL, Townsend CA (2002) A flexible route to (5R)-thiolactomycin a naturally occurring inhibitor of fatty acid synthesis. Org Lett 4:3859–3862CrossRefPubMedGoogle Scholar
  39. Misset-Smits M, van Ophem PW, Sakuda S, Duine JA (1997) Mycothiol, 1-O-(2′-[N-acetyl-l-cysteinyl]amido-2′deoxy-α-d-glucopyranosyl-d-myo-inositol, is the factor of NAD/factor dependent formaldehyde dehydrogenase. FEBS Lett 409:221–222CrossRefPubMedGoogle Scholar
  40. Mitchell RE, Durbin RD (1981) Tagetitoxin, a toxin produced by Pseudomonas syringae pv tagetis: purification and partial characterization. Physiol Plant Pathol 18:157–168Google Scholar
  41. Mitchell RE, Coddington JM, Young H (1989) A revised structure for tagetitoxin. Tetrahedron Lett 30:501–504CrossRefGoogle Scholar
  42. Miyakawa S, Suzuki K, Noto T, Haranda Y, Okazaki H (1982) Thiolactomycin a new antibiotic. IV. Biological properties and chemotherapeutic activity in mice. J Antibiot (Tokyo) 35:411–419Google Scholar
  43. Moynihan HA, Roberts SM (1994) Preparation of some novel S-nitroso compounds as potential slow-release agents for nitric oxide in vivo. J Chem Soc Perkin Trans I:797–805CrossRefGoogle Scholar
  44. Newton GL, Arnold K, Price MS, Sherrill C, delCardayre SB, Aharonowitz Y, Cohen G, Davies J, Fahey RC, Davis C (1996) Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes. J Bacteriol 178:1990–1995PubMedGoogle Scholar
  45. Newton GL, Unson MD, Anderberg SJ, Aguilera JA, Oh NN, delCardayre SB, Av-Gay Y, Fahey RC (1999) Characterization of Mycobacterium smegmatis mutants defective in 1-d-myo-inosityl-2-amino-2-deoxy-α-d-glucopyranoside and mycothiol biosynthesis. Biochem Biophys Res Commun 255:239–244CrossRefPubMedGoogle Scholar
  46. Newton GL, Av-Gay Y, Fahey RC (2000) A novel mycothiol-dependent detoxification pathway in mycobacteria involving mycothiol-S-conjugate amidase. Biochemistry 39:10739–10749CrossRefPubMedGoogle Scholar
  47. Nicholas GM, Bewley CA (2004) Inhibitors of mycothiol-S-conjugate amidase and related genes. Curr Med Chem Anti-Infect Agents 3:221–231CrossRefGoogle Scholar
  48. Nicholas GM, Kovac P, Bewley CA (2002) Total synthesis and proof of structure of mycothiol bimane. J Am Chem Soc 124:3492–3493CrossRefPubMedGoogle Scholar
  49. Oishi H, Noto T, Suzuki K, Hayashi T, Okazaki H, Ando K, Sawada M (1982) Thiolactomycin, a new antibiotic. I. Taxonomy of the producing organism fermentation and biological properties. J Antibiot (Tokyo) 35:391–395Google Scholar
  50. Patel MP, Blanchard JS (1998) Synthesis of des-myo-inositol mycothiol and demonstration of a mycobacterial specific reductase activity. J Am Chem Soc 120:11538–11539CrossRefGoogle Scholar
  51. Price AC, Choi K-H, Heath RJ, Li Z, White SW, Rock CO (2001) Inhibition of β-ketoacyl-[acyl carrier protein] synthases by thiolactomycin and cerulenin: structure and mechanism. J Biol Chem 276:6551–6559CrossRefPubMedGoogle Scholar
  52. Robina I, Vogel P (2002) Synthesis and biological properties of oligothiosaccharides. Curr Org Chem 6:1177–1214CrossRefGoogle Scholar
  53. Robina I, Vogel P, Witczak ZJ (2001) Synthesis and biological properties of monothiosaccharides. Curr Org Chem 5:1177–1214CrossRefGoogle Scholar
  54. Sareen D, Steffek M, Newton GL, Fahey RC (2002) ATP-dependent-l-cysteine: 1-d-myo-inosityl-2-amino-2-deoxy-α-d-glucopyranosideligase, mycothiol biosynthesis enzyme MshC, is related to class I cysteinyl-t-RNA synthetases. Biochemistry 41:6885–6890CrossRefPubMedGoogle Scholar
  55. Slayden RA, Lee RE, Armour JW, Cooper AM, Orme IM, Brennan PJ, Besra GS (1996) Antimicrobial action of thiolactomycin: an inhibitor of fatty acid and mycolic acid synthesis. Antimicrob Agents Chemother 40:2813–2819PubMedGoogle Scholar
  56. Steinberg TH, Mathews DE, Durbin RD, Burgess RR (1990) Tagetitoxin: a new inhibitor of eukaryotic transcription by RNA polymerase III. J Biol Chem 265:499–505PubMedGoogle Scholar
  57. Szczepina MG, Yuan Y, Johnston BD, Svensson B, Pinto BM (2004) Synthesis of alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol analogues: Polar side-chain modification, sulfonium and selenonium heteroatom variants, conformational analysis, and evaluation as glycosidase inhibitors. J Am Chem Soc 126:12458–12469CrossRefPubMedGoogle Scholar
  58. Trimboli D, Fahy PC, Baker KF (1978) Apical chlorosis and leaf spot of Tagetes spp. caused by Pseudomonas tagetis Hellmers. Aust J Agric Res 29:831–839Google Scholar
  59. Varela O (1997) Aldonolactones as chiral templates in the synthesis of thiolactones, 1,3-polyols and hydroxyl amino acids. Pure Appl Chem 69:621–626CrossRefGoogle Scholar
  60. Wang PG, Xian M, Tang X, Wu X, Wen Z, Cai T, Janczuk AJ (2002) Nitric oxide donors: chemical activities and biological applications. Chem Rev 102:1091–1134CrossRefPubMedGoogle Scholar
  61. Witczak ZJ (1999) Thio-sugars biological relevance as potential therapeutics. Curr Med Chem 6:165–178PubMedGoogle Scholar
  62. Witczak ZJ, Sun J, Mielguj R (1995) Synthesis of l-fucopyranosyl-4-S-thiodisaccharides from levoglucosenone and their inhibitory activity on l-fucosidase. Bioorg Med Chem Lett 5:2169–2171CrossRefGoogle Scholar
  63. Witczak ZJ, Chhabra R, Chen H, Xie X-Q (1997) Thio-sugars II. A novel approach to thiodisaccharides. The synthesis of 3-deoxy-4-thiocellobiose from levoglucosenone. Carbohydr Res 301:167–175CrossRefGoogle Scholar
  64. Witczak ZJ, Chen H, Kaplon P (2000a) Thio-sugars V. From d-glucal to 3-deoxy-(1–2)-2-S-thiodisaccharides through isolevoglucosenone a simple approach. Tetrahedron Asymmetry 11:519–532CrossRefGoogle Scholar
  65. Witczak ZJ, Chhabra R, Boryczewski D (2000b) Thio-sugars III. Stereoselective approach to β-(1–2)-2,3-dideoxy-3-C-acetamidomethyl-2-S-thiodisaccharides from levoglucosen-one. J Carbohydr Chem 19:543–553CrossRefGoogle Scholar
  66. Witczak ZJ, Kaplon P, Kolodziej M (2002) Thio-sugars VI. A simple stereoselective approach to (1–3)-S-thiodisaccharides from levoglucosenone. Monatsh Chem 133:521–539CrossRefGoogle Scholar
  67. Witczak ZJ, Kaplan P, Dey PM (2003) Thio-sugars VII. Effects of α-(1–4)-3′-deoxythiodisaccharides and their sulfoxides and sulfones on the viability and growth of selected murine and human tumor cell line. Carbohydr Res 338:11–18CrossRefPubMedGoogle Scholar
  68. Xu W, Springfield SA, Koh JT (2000) Highly efficient synthesis of 1-thioglycosides in solution and solid phase using iminophosphorane bases. Carbohydr Res 325:169–176CrossRefPubMedGoogle Scholar
  69. Yoshikawa M, Murakami T, Shimada H, Matsuda H, Yamahara J, Tanabe G, Muraoka O (1997) Salacinol, potent antidiabetic principle with unique thiosugar sulfonium sulfate structure from the Ayurvedic traditional medicine Salacia reticulata in Sri Lanka and India. Tetrahedron Lett 38:8367–8370CrossRefGoogle Scholar
  70. Yoshikawa M, Murakami T, Yashiro K, Matsuda H (1998) Kotalanol, a potent a-glucosidase inhibitor with thiosugar sulfonium sulfate structure, from antidiabetic Ayurvedic medicine Salacia reticulata. Chem Pharm Bull 46:1339–1340PubMedGoogle Scholar
  71. Yu HN, Ling C-C, Bundle DR (2001) Efficient stereoselective synthesis of 1-thio-β-mannopyranosides. J Chem Soc Perkin Trans 1:832–837CrossRefGoogle Scholar
  72. Zhu X, Schmidt RR (2004) Efficient synthesis of S-linked glycopeptides in aqueous solution by a convergent strategy. Chem Eur J 10:875–887CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesNesbitt School of Pharmacy, Wilkes UniversityWilkes-BarreUSA

Personalised recommendations