VZL 2010, 79(1):15-22

Beta-Amino Acids and Their Natural Biologically Active Derivatives. I. Derivatives of Beta-Alanine and Beta-Leucine

Jiří Patočka ORCID...
Jihočeská univerzita v Českých Budějovicích, Zdravotně sociální fakulta, katedra radiologie a toxikologie, České Budějovice

Na rozdíl od proteinogenních α-aminokyselin, které jsou základem všech proteinů a enzymů kontrolujících metabolismus v živé materii, většina β-aminokyselin se vyskytuje pouze jako součást omezeného počtu přírodních látek. Jak se zdá, zejména bakterie, cyanobakterie, houby a rostliny často imkorporují β-aminokyseliny do svých sekundárních metabolitů. Nejvýznamnějšími β-aminokyselinami jsou β-alanin, β-leucin, β-lysin, β-arginin, β-glutamát, β-phenylalanin a β-tyrosin.
Beta-alanin je přírodní aminokyselina, která však není využívána při biosyntéze žádných důležitých proteinů a enzymů. Přesto je β-alanin nejrozšířenější β-aminokyselinou. Byl nalezen u živočichů, rostlin, hub i bakterií, neboť je zabudován do látek jejich primárního i sekundárního metabolismu. U savců je β-alanin součástí přirozeně se vyskytujících dipeptidů karnosinu a anserinu, které jsou důležitými molekulami jejich primárního metabolismu, a také kyseliny pantotenové (vitamin B5), která sama je součástí koenzymu A. Některé sekundární metabolity β-alaninu jsou biologicky velmi aktivní sloučeniny, které byly nejprve nalezeny v rostlinách a suchozemských bakteriích a později, počínaje rokem 1980, v mořských houbách a cyanobakteriích (sinicích), které se staly významným předmětem výzkumu. Tyto organismy velmi často obsahují cyklické a acyklické peptidy a depsipeptidy s neobvyklými aminokyselinani. Přírodní látky se zabudovaným β-alaninem představují substance zajímající jak akademické, tak průmyslové chemiky, farmakology a toxikology. Neobyčejně významné jsou tyto látky pro všechny, kteří se zajímají o bioorganickou a biologickou chemii. Přírodní deriváty β-leucinu jsou méně početné, ale četné nálezy B12-dependentní 2,3-aminomutáz u bakterií, rostlin i savců podporují myšlenku většího rozšíření přírodních látek s β-leucinovým motivem.

Keywords: Beta-alanin; Přírodní látky; Anserin; Karnosin; Barangamid; Destruxin; Kryptofycin; Leualacin; Leucinostatin; Theonellamid; Theonellapeptolid; Yanucamid

Contrary to proteinogenic α-amino acids that are constituents of all proteins and enzymes which control the metabolism in living matter, most β-amino acids only occur as constituents of distinct natural compounds. Apparently, bacteria, cyanobacteria, fungi, and plants often incorporate β-amino acids into secondary metabolites. The most important β-amino acids are β-alanine, β-leucine, β-lysine, β-arginine, β-glutamate, β-phenylalanine and β-tyrosine.Beta-alanine is a naturally occurring amino acid which is not used in the biosynthesis of any major proteins or enzymes. Beta-Alanine is the most widespread of all β-amino acids. It has been found in animals, plants, fungi, and bacteria because it is incorporated in compounds of the primary and secondary metabolism. In mammals, β-alanine is a component of the naturally occurring dipeptides carnosine and anserine which are important molecules of their primary metabolism and also of pantothenic acid (vitamin B5) which itself is a component of coenzyme A. Multiple secondary metabolites of β-alanine are biologically very active compounds which were primarily found in plants and terrestrial bacteria and later, starting with the 1980s, in marine sponges and cyanobacteria which became important subjects of investigation. These organisms often contain cyclic and acyclic peptides and depsipeptides with unusual amino acid moieties. Natural compounds with incorporated β-alanine represent substances of interest to both academic and industrial chemists, pharmacologists, and toxicologists. Exceedingly important are these compounds for all who are interested in bioorganic and biological chemistry. Beta-Leucine natural derivatives are less numerous but finding of B12-dependent 2,3-aminomutase in bacteria, plants, and mammals provides an idea of better spread compounds with β-leucine moiety in nature.

Keywords: Beta-Alanine; Beta-Leucine; Natural compounds; Anserine; Carnosine; Barangamide; Destruxin; Cryptophycine; Leualacine; Leucinostatin; Theonellamide; Theonellapeptolide; Yanucamide

Received: September 30, 2009; Published: March 1, 2010  Show citation

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Patočka, J. (2010). Beta-Amino Acids and Their Natural Biologically Active Derivatives. I. Derivatives of Beta-Alanine and Beta-Leucine. Vojenské Zdravotnické Listy, 79(1), 15-22
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    References

    1. BOLDYREV, AA. - STVOLINSKY, SL. - TYULINA, OV., et al. Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals. Cell. Mol. Neurobiol., 1997, vol. 17, no. 2, p. 259-271. Go to original source... Go to PubMed...
    2. BRADFISCH, GA. - HARMER, SL. Omega-Conotoxin GVIA and nifedipine inhibit the depolarizing action of the fungi metabolite, destruxin B on muscle from the tobacco budworm (Heliothis virescens). Toxicon, 1990, vol. 28, no. 11, p. 1249-1254. Go to original source... Go to PubMed...
    3. COX, PA. - BANACK, SA. - MURCH, SJ., et al. Diverse taxa of cyanobacteria produce β-N-methylamino-L-alanine, a neurotoxic amino acid. Proc. Nat. Acad. Sci. USA, 2005, vol. 102, no. 27, p. 5074-5078. Go to original source... Go to PubMed...
    4. CSERMELY, P. - RADICS, L. - ROSSI, C., et al. The nonapeptide leucinostatin A acts as a weak ionophore and as immunosuppressant on T lymphocytes. Biochim. Biophys. Acta, 1994, vol. 1221, no. 2, p. 125-132. Go to original source... Go to PubMed...
    5. DEWI, AS. Biologically active secondary metabolites from tropical marine invertebrates (Thesis). Canada, University of British Columbia, 2009. 104 p.
    6. EISSLER, S. - STONCIUS, A. - NAHRWOLD, M., et al. The synthesis of cryptophycins. Synthesis, 2006, no 22, p. 3747-3789. Go to original source...
    7. FREY, PA. - HEGEMAN, AD. - RUZICKA, FJ. The radical SAM superfamily. Crit. Rev. Biochem. Mol. Biol., 2008, vol. 43, no. 1, p. 63-88. Go to original source... Go to PubMed...
    8. GODDARD, AW. - MASON, GF. - ALMAI, A., et al. Reductions in occipital cortex GABA levels in panic disorder detected with 1H-magnetic resonance spectroscopy. Arch. Gen. Psychiatry, 2001, vol. 58, no. 6, p. 556-561. Go to original source... Go to PubMed...
    9. GRIFFITH, OW. Beta-amino acids: mammalian metabolism and utility as alpha-amino acid analogues. Annu. Rev. Biochem., 1986, vol. 55, p. 855-878. Go to original source... Go to PubMed...
    10. HAEFNER, B. Deep-sea natural products. Drug Disc. Today, 2003, vol. 8, no. 12, p. 536-544. Go to original source... Go to PubMed...
    11. HAMANO, K. - KINOSHITA, M. - FURUYA K., et al. Leualacin, a novel calcium blocker from Hapsidospora irregularis. II. Structure determination. J. Antibiot., 1992b. vol. 45, no. 6, p. 906-913. Go to original source... Go to PubMed...
    12. HAMANO, K. - KINOSHITA. M. - TANZAWA, K., et al. Leualacin, a novel calcium blocker from Hapsidospora irregularis. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties. J. Antibiot., 1992a, vol. 45, no. 6, p. 899-905. Go to original source... Go to PubMed...
    13. HIPKISS, AR. - BROWNSON, C. - CARRIER, MJ. Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech. Ageing Dev., 2001, vol. 122, no. 13, p. 1431-1445. Go to original source... Go to PubMed...
    14. HIPKISS, AR. Chapter 3 carnosine and its possible roles in nutrition and health. Adv. Food Nutr. Res., 2009, vol. 57, p. 87-154. Go to original source... Go to PubMed...
    15. HO, CH. - MAGTANOG, L. - BARKER. SL., et al. A molecular barcoded yeast ORF library enables mode-of-action analysis of bioactive compounds. Nature Biotechnol., 2009, vol. 27, no. 4, p. 369-377. Go to original source... Go to PubMed...
    16. HU, MK. - YANG, FC. - CHOU, CC., et al. Synthesis and evaluation of backbone/amide-modified analogs of leualacin. Bioorg. Med. Chem. Lett., 1999, vol. 9, no. 4, p. 563-568. Go to original source... Go to PubMed...
    17. HU, QB. - AN, XC. - JIN, FL., et al. Toxicities of destruxins against Bemisia tabaci and its natural enemy, Serangium japonicum. Toxicon, 2009, vol. 53, no. 1, p. 115-121. Go to original source... Go to PubMed...
    18. CHOI, SY. - KWON, HY. - KWON OB., et al. Hydrogen peroxide-mediated Cu, Zn-superoxide dismutase fragmentation: protection by carnosine, homocarnosine and anserine. Biochim. Biophys. Acta, 1999, vol. 1472, no. 3, p. 651-657. Go to original source... Go to PubMed...
    19. ISHIGURO, K. - ARAI, T. Action of the peptide antibiotik leucinostatin. Antimicrob. Agents Chemother., 1976, vol. 9, no. 6, p. 893-898. Go to original source... Go to PubMed...
    20. JACKSON, MC. - LENNEY, JF. The distribution of carnosine and related dipeptides in rat and human tissues. Inflamm. Res., 1996, vol. 45, no 3, p. 132-135. Go to original source... Go to PubMed...
    21. KARAMYAN, VT. - SPETH, RC. Animals models of BMAA neurotoxicity: a critical review. Life Sci., 2008, vol. 82, no. 5/6, p. 233-246. Go to original source... Go to PubMed...
    22. KOBAYASHI, M. - KANZAKI, K. - KATAYAMA, S., et al. Marine natural products. XXXIII. Theonellapeptolide IId, a new tridecapeptide lactone from the Okinawan marine sponge Theonella swinhoei. Chem. Pharm. Bull. (Tokyo), 1994, vol. 42, no. 12, p. 1410-1415. Go to original source... Go to PubMed...
    23. KOBAYASHI, M. - LEE, NK. - SHIBUYA, H., et al. Marine natural products. XXVI. Biologically active tridecapeptide lactones from the Okinawan marine sponge Theonella swinhoei (Theonellidae). 2. Structures of theonellapeptolides Ia, Ib, Ic, and Ie. Chem. Pharm. Bull. (Tokyo), 1991, vol. 39, no. 5, p. 1177-1184. Go to original source... Go to PubMed...
    24. KODAIRA, Y. Toxic substances to insects produced by Aspergillus ochraceus and Oospora destructor. Agric. Biol. Chem., 1961, vol. 25, no. 3, p. 261-262. Go to original source...
    25. LI, S. - DUMDEI, EJ. - BLUNT, JW., et al. Theonellapeptolide IIIe, a new cyclic peptolide from the New Zealand deep water sponge Lamellomorpha strongylata. J. Nat. Prod., 1998, vol. 61, no. 6, p. 724-728. Go to original source... Go to PubMed...
    26. LIANG, J. - MOORE, RE. - MOHER, ED., et al. Cryptophycins-309, 249 and other cryptophycin analogs: Preclinical efficacy studies with mouse and human tumors. Invest. New Drugs, 2005, vol. 23, no. 3, p. 213-224. Go to original source... Go to PubMed...
    27. LIRA, SP. - VITA-MARQUES AM. - SELEGHIM, MH., et al. New destruxins from the marine-derived fungus Beauveria felina. J. Antibiot. (Tokyo), 2006, vol. 59, no. 9, p. 553-563. Go to original source... Go to PubMed...
    28. LIU, X. - RUSH, T. - ZAPATA, J., et al. Beta-N-methylamino-l-alanine induces oxidative stress and glutamate release through action on system Xc(-). Exp. Neurol., 2009, vol. 217, no. 2, p. 429-433. Go to original source... Go to PubMed...
    29. MIKAMI, Y. - FUKUSHIMA, K. - ARAI, T., et al. Leucinostatins, peptide mycotoxins produced by Paecilomyces lilacinus and their possible roles in fungal infection. Zentralbl. Bakteriol. Mikrobiol. Hyg. [A], 1984, vol. 257, no. 2, p. 275-283. Go to original source...
    30. MINTO, RE. - BLACKLOCK, BJ. Biosynthesis and function of polyacetylenes and allied natural products. Progr. Lipid Res., 2008, vol. 47, no. 4, p. 233-306. Go to original source... Go to PubMed...
    31. MISONO, Y. - ITO, A. - MATSUMOTO, J., et al. Physarigins A-C, three new yellow pigments from a cultured myxomycete Physarum rigidum. Tetrahedron Lett., 2003, vol. 33, no. 24, p. 4479-4481. Go to original source...
    32. MORI, Y. - TSUBOI, M. - SUZUKI, M., et al. Structure of leucinostatin A, new peptide antibiotic from Paecilomyces lilacinus A-267. J. Chem. Soc. Chem. Commun., 1982, p. 94-96. Go to original source...
    33. OHTA, E. - OKADA, H. - OHTA S., et al. Tridecapeptide lactone from a marine sponge Petrosia species, through disturbance of cortical F-actin distribution. Biosci. Biotechnol. Biochem., 2003, vol. 67, no. 9, p. 1908-1915. Go to original source... Go to PubMed...
    34. PATOČKA, J. Co to jsou theonellapeptolidy? Bull. ČSBMB, 2002, vol. 30, p. 33-34.
    35. PATOČKA, J. Některé méně známé neuromediátory a neuromodulátory v CNS. Psychiatrie, 2002, vol. 6, suppl. 3, p. 36-40.
    36. PATOČKA, J. - STRUNECKÁ, A. - STIBOROVÁ, M. Inhibitory microtubulů (Microtubule inhibitors). Chem. Listy, 2001, vol. 95, no. 11, p. 700-707.
    37. PEGGION, E. - MAMMI, S. - SCHIEVANO, E., et al. Structure-function studies of analogues of parathyroid hormone (PTH)-1-34 containing beta-amino acid residues in positions 11-13. Biochemistry, 2002, vol. 41, no. 25, p. 8162-875. Go to original source... Go to PubMed...
    38. PORTER, EA. - WANG, X. - LEE, HS., et al. Antibiotics: Non-haemolytic β-amino-acid oligomers. Nature, 2000, vol. 404, no. 6778, p. 565. Go to original source... Go to PubMed...
    39. PŘEROSTOVÁ, S. Není nouze jako nouze: Porovnání odpovědi rostlinné buňky na solný stres, obecný osmotický stres a nedostatek vody (bakalářská práce). Přírodovědecká fakulta UK, Praha, 2009. 27 s.
    40. RAO, SD. - BANACK. SA. - COX, PA., et al. BMAA selectively injures motor neurons via AMPA/kainate receptor activation. Exp. Neurol., 2006, vol. 201, no. 1, p. 244-252. Go to original source... Go to PubMed...
    41. ROY, MC. - OHTANI, IO. - ICHIBA, T., et al. New cyclic peptides from the Indonesian sponge Theonella swinhoei. Tetrahedron, 2000, vol. 56, no. 46, p. 9079-9092. Go to original source...
    42. ROY, MC. - OTANI, IO. - TANAK, J., et al. A new cyclic peptide from the sponge Theonella cf. swinhoei, collected at Baranglompo, Indonesia. Nippon Kag. Koen. Yokoshu, 1999, vol. 76, no. 2, p. 706.
    43. SANTUCCI, S. - ZSÜRGER, N. - CHABRY, J. Beta-N-methylamino-L-alanine induced in vivo retinal cell death. J. Neurochem., 2009, vol. 109, no. 3, p. 819-825. Go to original source... Go to PubMed...
    44. SASSOE-POGNETTO, M. - CANTINO, D. - PANZANELLI, P., et al. Presynaptic co-localization of carnosine and glutamate in olfactory neurones. Neuroreport, 1993, vol. 5, no. 1, p. 7-10. Go to original source... Go to PubMed...
    45. SETYOWATI, EP. - SUDARSONO, UAJ. - KARDONO, LBS., et al. Theonellapeptolide In Structure identification of cytotoxic constituent from Kaliapsis sp. Sponge (Bowerbank) collected from West Bali Sea Indonesia. J. Biol. Sci., 2009, vol. 9, no. 1, p. 29-36. Go to original source...
    46. SITACHITTA, N. - WILLIAMSON, RT. - GERWICK, WH. Yanucamides A and B, two new depsipeptides from an assemblage of the marine cyanobacteria Lyngbya majuscula and Schizothrix species. J. Nat. Prod., 2000, vol. 63, no. 2, p. 197-200. Go to original source... Go to PubMed...
    47. SPENCER, PS. - NUNN, PB. - HUGON, J., et al. Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science, 1987, vol. 237, no. 4814, p. 517-522. Go to original source... Go to PubMed...
    48. STEER, DL. - LEW, RA. - PERLMUTTER, P., et al. Beta-amino acids: versatile peptidomimetics. Curr. Med. Chem., 2002, vol. 9, no. 8, p. 811-822. Go to original source... Go to PubMed...
    49. STOUT, JR. - CRAMER, JT. - ZOELLER, RF., et al. Effects of beta-alanine supplementation on the onset of neuromuscular fatigue and ventilatory threshold in women. Amino Acids, 2007, vol. 32, no. 3, p. 381-386. Go to original source... Go to PubMed...
    50. TSUDA, M. - SHIMBO, K. - KUBOTA, T., et al. Two theonellapeptolide congeners from marine sponge Theonella sp. Tetrahedron, 1999, vol. 55, no. 34, p. 10305-10314. Go to original source...
    51. TSUNOO, A. - KAMIJO, M. - TAKETOMO, N., et al. Roseocardin, a novel cardiotonic cyclodepsipeptide from Trichothecium roseum TT103. J. Antibiot. (Tokyo), 1997, vol. 50, no. 12, p. 1007-1013. Go to original source... Go to PubMed...
    52. WADA, S. - MATSUNAGA, S. - FUSETANI, N., et al. Accumulation of H+ in vacuoles induced by marine peptide toxin, theonellamide F, in rat embryonic 3Y1 fibroblasts. Marine Biotechnol., 2002, vol. 1, no. 4, p. 571-582. Go to original source... Go to PubMed...
    53. WADA, S. - MATSUNAGA, S. - FUSETANI, N., et al. Theonellamide F, a bicyclic peptide marine toxin, induces formation of vacuoles in 3Y1 rat embryonic fibroblast. Marine Biotechnol., 1999, vol. 1. p. 337-341. Go to original source... Go to PubMed...
    54. WAISSER, K. Organická chemie I. Praha, Karolinum, 1999. 339 s.
    55. WASE, NV. - WRIGHT, PC. Systems biology of cyanobacterial secondary metabolite production and its role in drug discovery. Expert Opin. Drug Discov., 2008, vol. 3, no. 8, p. 903-929. Go to original source... Go to PubMed...
    56. ŽABKA, M. - DRASTICHOVÁ, K. - JEGOROV, A., et al. Direct evidence of plant-pathogenic activity of fungal metabolites of Trichothecium roseum on apple. Mycopathologia, 2006, vol. 162, no. 1, p. 65-68. Go to original source... Go to PubMed...

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