Skip to main content
SpringerLink
Log in

The Discovery of MAP30 and Elucidation of its Medicinal Activities

  • Chapter
  • First Online:
Book cover Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds

Abstract

In this chapter, we review the discovery of MAP30, a novel multifunctional antiviral and anti-tumor plant protein, and elucidation of its medicinal properties. MAP30, M omordica A ntiviral P rotein 30 kD, is isolated from the medicinal plant Momordica charantia. Biochemical and biophysical studies have yielded important insights into the structure, function and mechanism of MAP30. Column chromatography by ionic exchange, affinity binding and size fractionation were applied for the isolation and purification of MAP30. Protein and nucleotide sequencing were used to elucidate the structure of this protein and its gene. The gene encoding MAP30 was cloned and expressed by recombinant technology. Structure activity mapping was performed using 3D-structure determination, bioinformatics and molecular modeling, together with bioactivity confirmation. Results from these studies demonstrate how cutting-edge modern approaches can be applied to discover medicinal activities from natural products and to define their molecular structure, biological function, and mechanisms of action.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Robinson MM, Zhang X (2011) Traditional medicines, issues and challenges. WHO, Geneva

    Google Scholar 

  2. Eisenberg DM, Davis RB, Ettner SL, Appel S, Wilkey SA, Van Rompay M, Kessler RC (1998) Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 280:1569–1575

    Article  PubMed  CAS  Google Scholar 

  3. Eisenberg DM, Kessler RC, Foster C, Norlock FE, Calkins DR, Delbanco TL (1993) Unconventional medicine in the United States. Prevalence, costs, and patterns of use. N Engl J Med 328(4):246–252

    Article  PubMed  CAS  Google Scholar 

  4. Wolsko PM, Eisenberg DM, Davis RB, Ettner SL, Phillips RS (2002) Insurance coverage, medical conditions, and visits to alternative medicine providers: results of a national survey. Arch Intern Med 162(3):281–287

    Article  PubMed  Google Scholar 

  5. Eisenberg DM, Kessler RC, Van Rompay MI, Kaptchuk TJ, Wilkey SA, Appel S, Davis RB (2001) Perceptions about complementary therapies relative to conventional therapies among adults who use both: results from a national survey. Ann Intern Med 135(5):344–351

    PubMed  CAS  Google Scholar 

  6. Kessler RC, Davis RB, Foster DF, Van Rompay MI, Walters EE, Wilkey SA, Kaptchuk TJ, Eisenberg DM (2001) Long-term trends in the use of complementary and alternative medical therapies in the United States. Ann Intern Med 135(4):262–268

    PubMed  CAS  Google Scholar 

  7. Nahin RL, Barnes PM, Stussman BJ, Bloom B (2009) Cost of CAM and frequency of visits to CAM prectitioners: United States, 2007 National health statistics reports; no 18. National Center for Health Statistics, Hyattsville

    Google Scholar 

  8. Lee-Huang S, Huang PL, Zhang D, Lee JW, Bao J, Sun YT, Chang Y-T, Zhang J, Huang PL (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part I. Fusion inhibition. Biochem Biophys Res Commun 354:872–878

    Article  PubMed  CAS  Google Scholar 

  9. Lee-Huang S, Huang PL, Zhang D, Lee JW, Bao J, Sun YT, Chang Y-T, Zhang J, Huang PL (2007) Discovery of small-molecule HIV-1 fusion and integrase inhibitors oleuropein and hydroxytyrosol: Part II. Integrase inhibition. Biochem Biophys Res Commun 354:879–884

    Article  PubMed  CAS  Google Scholar 

  10. Bao J, Zhang DW, Zhang JZH, Huang PL, Huang PL, Lee-Huang S (2007) Computational study of bindings of olive leaf extract (OLE) to HIV-1 fusion protein gp41. FEBS Lett 581:2737–2742

    Article  PubMed  CAS  Google Scholar 

  11. Lee-Huang S, Zhang L, Huang PL, Chang YT, Huang PL (2003) Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem Biophys Res Commun 307:1029–1037

    Article  PubMed  CAS  Google Scholar 

  12. Lee-Huang S, Maiorov V, Huang PL, Lee HC, Ng A, Chang Y-T, Kallenbach N, Huang PL, Chen HC (2005) Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity. Biochemistry 44:4648–4655

    Article  PubMed  CAS  Google Scholar 

  13. Lee-Huang S, Huang PL, Huang PL, Sun YT, Kung HF, Blithe DL, Chen HC (1999) Lysozyme and ribonucleases as anti-HIV components in beta-core preparations of hCG. Proc Natl Acad Sci U S A 96:2678–2681

    Article  PubMed  CAS  Google Scholar 

  14. Bourinbaiar AS, Lee-Huang S (1995) Anti-HIV effect of beta subunit of human chorionic gonadotropin (βhCG) in vitro. Immunol Let 44:13–18

    Article  CAS  Google Scholar 

  15. Lee-Huang S, Huang PL, Nara PL, Chen HC, Kung HF, Huang P, Huang HI, Huang PL (1990) MAP 30: a new inhibitor of HIV-1 infection and replication. FEBS Letts 272:12–18

    Article  CAS  Google Scholar 

  16. Lee-Huang S, Huang PL, Kung HF, Li BQ, Huang PL, Huang P, Huang HI, Huang PL, Chen HC (1991) TAP 29: an anti-human immunodeficiency virus protein from Trichosanthes kirilowii that is nontoxic to intact cells. Proc Natl Acad Sci U S A 88:6570–6574

    Article  PubMed  CAS  Google Scholar 

  17. Lee-Huang S, Kung HF, Huang PL, Huang PL, Li B-Q, Huang P, Huang HI, Chen HC, Huang PL (1991) A new class of anti-HIV agents: GAP 31, DAP 30 and DAP 32. FEBS Letts 291:139–144

    Article  CAS  Google Scholar 

  18. Huang PL, Sun YT, Chen HC, Huang PL, Lee-Huang S (1999) Proteolytic fragments of anti-HIV and anti-tumor proteins MAP30 and GAP31 are biologically active. Biochem Biophys Res Commun 262:615–623

    Article  PubMed  CAS  Google Scholar 

  19. Lee-Huang S, Huang PL, Chen HC, Huang PL, Bourinbaiar AS, Huang HI, Kung HF (1995) Anti-HIV and anti-tumor activities of recombinant MAP 30 of bitter melon. Gene 161:151–156

    Article  PubMed  CAS  Google Scholar 

  20. Arazi T, Huang PL, Huang PL, Zhang L, Shiboleth YM, Gal-On A, Lee-Huang S (2002) Production of antiviral and antitumor proteins MAP30 and GAP31 in cucurbits using the plant virus vector ZYMV–AGII. Biochem Biophys Res Commun 292:441–448

    Article  PubMed  CAS  Google Scholar 

  21. Rybak SM, Lin JJ, Newton DL, Kung HF, Monks A, Chen HC, Huang PL, Huang PL, Lee-Huang S (1994) In vitro anti-tumor activity of the plant ribosome inactivating proteins MAP 30 and GAP 31. Int J Onc 5:1171–1176

    CAS  Google Scholar 

  22. Lee-Huang S, Huang PL, Sun YT, Kung HF, Huang PL, Murphy WJ (2000) Inhibition of human breast tumor MDA-MB-231 xenografts and HER2 expression in SCID mice by anti-tumor agents GAP31 and MAP30. Anticancer Res 20:653–659

    Google Scholar 

  23. Lee-Huang S, Huang PL, Chen HC, Kung HF, Nara PL, Li BQ, Huang PL, Huang HI, Huang PL (1992) Plant proteins with antiviral activity against HIV. In: Chu CK, Cutler HG (eds) Natural products as antiviral agents. Plenum, New York, pp 153–170

    Chapter  Google Scholar 

  24. Schreiber CA, Sun YT, Wan L, Krey LC, Lee-Huang S (1999) Anti-HIV agents, MAP30 and GAP31 are not toxic to human spermatocytes: potential use of these agents against sexual transmission of HIV-1. Steril Ferti 72:686–690

    Article  CAS  Google Scholar 

  25. Lee-Huang S, Huang PL, Kong XP, Schapira M, Huang PL (2003) Novel anti-HIV and anti-tumor proteins MAP30 and GAP31: molecular, biochemical and structural insights into biological activities and mechanism. Recent Res Devel Biophys Biochem 81:235–257

    Google Scholar 

  26. Bourinbaiar AS, Lee-Huang S (1995) Potentiation of anti-HIV activity of anti-inflammatory drugs dexamethasone and indomethacin, by MAP 30, the antiviral agent from bitter melon. Biochem Biophys Res Commun 208:779–785

    Article  PubMed  CAS  Google Scholar 

  27. Bourinbaiar AS, Lee-Huang S (1996) The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against herpes simplex virus infection in vitro. Biochem Biophys Res Commun 219:923–929

    Article  PubMed  CAS  Google Scholar 

  28. Sun YT, Huang PL, Li JJ, Huang YQ, Zhang L, Huang PL, Lee-Huang S (2001) Anti-HIV agent MAP30 modulates the expression profile of viral and cellular genes for proliferation and apoptosis in AIDS-related lymphoma cells infected with kaposi’s sarcoma-associated virus. Biochem Biophys Res Commun 287:983–994

    Article  PubMed  CAS  Google Scholar 

  29. Huang PL, Chen HC, Kung HF, Huang PL, Huang P, Huang HI, Lee–Huang S (1992) Anti-HIV plant proteins catalyze topological changes of DNA into inactive forms. BioFactors 4:37–41

    PubMed  CAS  Google Scholar 

  30. Lee-Huang S, Kung HF, Huang PL, Bourinbaiar AS, Morell JL, Brown JH, Huang PL, Tsai WP, Chen AY, Huang HI, Chen HC (1994) HIV-1 inhibition, DNA binding, RNA binding and ribosome inactivation activities in the N-terminal segments of the plant anti-HIV protein GAP 31. Proc Natl Acad Sci U S A 91:12208–12212

    Article  PubMed  CAS  Google Scholar 

  31. Lee-Huang S, Huang PL, Huang PL, Bourinbaiar AS, Chen HC, Kung HF (1995) Inhibition of HIV-1 integrase by plant antiviral proteins MAP 30 and GAP 31. Proc Natl Acad Sci U S A 92:8818–8822

    Article  PubMed  CAS  Google Scholar 

  32. Lee-Huang S, Kung HF, Chen HC, Huang PL, Rybak SM, Huang PL, Bourinbaiar AS, Musayev F, Liaw YC (1994) Crystallization and preliminary X-ray analysis of GAP 31: an anti-HIV protein. J Mol Biol 240:92–94

    Article  PubMed  CAS  Google Scholar 

  33. Wang YX, Nouri N, Jacob J, Palmer I, Stahl SJ, Kaufman JD, Huang PL, Huang PL, Heather E, Pommier Y, Wingfield PT, Lee-Huang S, Bax A, Torchia DA (1999) Solution structure of anti-HIV and anti-tumor protein MAP30: structural insights into its multiple functions. Cell 99:433–442

    Article  PubMed  CAS  Google Scholar 

  34. Wang YX, Jacob J, Wingfield PT, Palmer I, Stahl SJ, Kaufman JD, Huang PL, Huang PL, Lee-Huang S, Torchia DA (2000) Anti-HIV and anti-tumor protein MAP30, a 30 kDa single strand type-1 RIP, shares similar secondary structure and β-sheet topology with the A chain of ricin, a type-II RIP. Prot Sci 9:138–144

    Article  CAS  Google Scholar 

  35. Wang XY, Marquardt J, Wingfield P, Stahl SJ, Lee-Huang S, Torchia D, Bax A (1999) Simultaneous measurement of 1H–15N, 1H–13C′ and 15N–13C′ dipole coupling in a perdeuterated 30 kDa protein dissolved in a dilute liquid crystalline phase. J Am Chem Soc 120:7385–7386

    Article  Google Scholar 

  36. Wang XY, Jacob J, Cordier F, Wingfield P, Stahl SJ, Lee-Huang S, Torchia D, Grzesiek S, Bax A (1999) Measurement of (3 h)J(NC′) connectivities across hydrogen bonds in a 30 kDa protein. J Biomol NMR 14:181–184

    Article  PubMed  CAS  Google Scholar 

  37. Huang PL, Huang PL, Lee-Huang S (2010) Oleuropein and related compounds reduce atherosclerosis. Open Conf Proc J 1:81–86

    Google Scholar 

  38. Lee-Huang S, Huang PL, Zhang D, Zhang JZH, Huang PL (2012) Oleuropein and related compounds from olive plants modulate adipogenesis. Open Conf Proc J (in press)

    Google Scholar 

  39. Hartono YD, Lee AN, Lee-Huang S, Zhang D (2011) Computational study of bindings of HL9, a nonapeptide fragment of human lysozyme, to HIV-1 fusion protein gp41. Bioorg Med Chem Lett 21:1607–1611

    Article  PubMed  CAS  Google Scholar 

  40. Lee-Huang S, Huang PL, Huang PL (2011) Live-cell real-time imaging reveals role of mitochondria in cell-to-cell transmission of HIV-1. Biochem Biophys Res Commun 415(2):384–389

    Article  PubMed  CAS  Google Scholar 

  41. Fang EF, Zhang CZ, Wong JH, Shen JY, Li CH, Ng TB (2012) The MAP30 protein from bitter gourd (Momordica charantia) seeds promotes apoptosis in liver cancer cells in vitro and in vivo. Cancer Lett 324(1):66–74 (Epub 9 May 2012)

    Google Scholar 

  42. Meng Y, Liu S, Li J, Meng Y, Zhao X (2012) Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica charantia L. with covalent conjugation of polyethyelene glycol. Int J Nanomed 7:3133–3142 (Epub 27 June 2012)

    Google Scholar 

Download references

Acknowledgments

Work done in this review was supported in part by NIH grants R01 AI31343, R01 AT01383, and by Blackout Funding. The authors are grateful to Helen C. Lin for her support and encouragement.

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA

    Sylvia Lee-Huang

  2. American BioScience, Boston, MA, USA

    Philip Lin Huang

  3. Department of Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA, 02114, USA

    Paul Lee Huang

Authors
  1. Sylvia Lee-Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philip Lin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul Lee Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sylvia Lee-Huang .

Editor information

Editors and Affiliations

  1. , Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Bayview Boulevard Street 251, Baltimore, 21224-6825, Maryland, USA

    Evandro Fei Fang

  2. , School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, Hong Kong SAR

    Tzi Bun Ng

Additional information

This Chapter is dedicated to the memory of Professor Severo Ochoa, our adored mentor, and to Dr. An Fu Lee, our beloved mother and grandmother, for their inspiration and encouragement.

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Lee-Huang, S., Lin Huang, P., Lee Huang, P. (2013). The Discovery of MAP30 and Elucidation of its Medicinal Activities. In: Fang, E., Ng, T. (eds) Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6214-5_8

Download citation

Publish with us

Policies and ethics

Search

Navigation