Abstract

Compounds with antiviral, antineoplastic, antifungal and antibacterial activities will be identified in marine species and their structures will be assigned. These include new components of the didemnin (antiviral, antineoplastic) and eudistomin (antiviral) complexes and an antineoplastic compound from Ecteinascidia turbinata, all from tunicates, as well as compounds from other tunicates and sponges. In addition, metabolites and quantitation of didemnin B will be studied in connection with its forthcoming clinical trials in cancer patients. Structures of a number of antibiotics will also be studied. These include the antifungal polyenes hamycin, aureofungin, and candimycin, as well as the non-polyenic antifungal macrolide desertomycin, the phospholipids quebemycin and 409 complex (antibacterial), the aromatic crisamicin (antineoplastic), and ficellomycin. Peptide antibiotics to be studied include saramycetin (antifungal), CC-1014B (cytotoxic), berninamycins A and B (antibacterial), antiamoebin, emerimicin, zervamicin, and alamethicin (all antibacterial and pore-forming). Bioactive compounds (antiviral) present in insects will also be identified and structural studies will be carried out on a Legionella pigment and a Pseudomonas growth factor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI004769-28
Application #
3124205
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1977-05-01
Project End
1990-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
28
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820

  Publications

Yuan, M; Namikoshi, M; Otsuki, A et al. (1999) Low-energy collisionally activated decomposition and structural characterization of cyclic heptapeptide microcystins by electrospray ionization mass spectrometry. J Mass Spectrom 34:33-43
Namikoshi, M; Yuan, M; Sivonen, K et al. (1998) Seven new microcystins possessing two L-glutamic acid units, isolated from Anabaena sp. strain 186. Chem Res Toxicol 11:143-9
Sakai, R; Rinehart, K L; Kishore, V et al. (1996) Structure--activity relationships of the didemnins. J Med Chem 39:2819-34
Sings, H L; Bible, K C; Rinehart, K L (1996) Acyl tunichlorins: a new class of nickel chlorins isolated from the Caribbean tunicate Trididemnum solidum. Proc Natl Acad Sci U S A 93:10560-5
Sakai, R; Rinehart, K L (1995) A new polyether acid from a cold water marine sponge, a Phakellia species. J Nat Prod 58:773-7
McGuire, J N; Wilson, S R; Rinehart, K L (1995) Cremeomycin, a novel cytotoxic antibiotic from Streptomyces cremeus. Structure elucidation and biological activity. J Antibiot (Tokyo) 48:516-9
An, J; Carmichael, W W (1994) Use of a colorimetric protein phosphatase inhibition assay and enzyme linked immunosorbent assay for the study of microcystins and nodularins. Toxicon 32:1495-507
Luukkainen, R; Namikoshi, M; Sivonen, K et al. (1994) Isolation and identification of 12 microcystins from four strains and two bloom samples of Microcystis spp.: structure of a new hepatotoxin. Toxicon 32:133-9
Guan, Y; Sakai, R; Rinehart, K L et al. (1993) Molecular and crystal structures of ecteinascidins: potent antitumor compounds from the Caribbean tunicate Ecteinascidia turbinata. J Biomol Struct Dyn 10:793-818
Namikoshi, M; Choi, B W; Sun, F et al. (1993) Chemical characterization and toxicity of dihydro derivatives of nodularin and microcystin-LR, potent cyanobacterial cyclic peptide hepatotoxins. Chem Res Toxicol 6:151-8

Showing the most recent 10 out of 28 publications