A new non-protein enediyne antibiotic N1999A2: Unique enediyne chromophore similar to neocarzinostatin and DNA cleavage feature

Tetrahedron Letters

Volumn 39, Issue 36, 1998, Pages 6495-6498

  Ando, Toshihiko ^a   Ishii, Makoto ^a   Kajiura, Takayuki ^a   Kameyama, Toshiyuki ^a   Miwa, Kiyoshi ^a   Sugiura, Yukio ^b  

^a AJINOMOTO CO INC   (Japan)

^b KYOTO UNIVERSITY   (Japan)

Author keywords

Antitumour compounds; Diynes; Natural products

Indexed keywords

AJ 9493; ANTIBIOTIC AGENT; ANTINEOPLASTIC ANTIBIOTIC; CALICHEAMICIN GAMMA1; DNA; DYNEMICIN A; ESPERAMICIN A1; N 1999A2; NATURAL PRODUCT; UNCLASSIFIED DRUG; ZINOSTATIN;

ARTICLE; CYTOTOXICITY; DNA BINDING; DNA CLEAVAGE; DRUG ACTIVITY; DRUG ISOLATION; DRUG STRUCTURE; NONHUMAN; STREPTOMYCES;

STREPTOMYCES; STREPTOMYCES SP.;

EID: 0032171502     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01383-5     Document Type: Article

References (8)

1. 1) Ishii, M.; Kajiura, T.; Ando, T.; Kameyama, T.; Miwa, K. (in preparation).
2. 2) Koide, Y.; Ishii, F.; Hasuda, K.; Koyama, Y.; Edo, K.; Katamine, S.; Ishida, N. J Antibiot. 1980, 33, 342-342.
3. 3) Edo, K.; Mizugaki, M.; Koide, Y.; Seto, H.; Furihata, K.; Otake, N.; Ishida, N. Tetrahedron Lett. 1985, 26, 331-334.
4. 4) The supernatant obtained by ammonium sulfate precipitation of the culture broth of Streptomyces sp. AJ9493 evidently showed strong cytotoxicity, but the precipitate presented only remarkably weak activity. In addition, this chromophore was not incorporated to the apoprotein of neocarzinostatin.
5. 32P-labeled 323-base pair restriction fragment (SalI/NruI) from plasmid pBR322 were conducted with N1999A2 (12.5-50 μM) and, separately, neocarzinostatin chromophore (10-40 μM) in the presence of dithiothreitol (20 mM) and calf thymus DNA (5 μg/ml) at 37°C and pH 7.0. Quantitative analysis of the DNA cleavage products was achieved by gel electrophoresis using a denaturing 10% polyacrylamide gel.
6. 6) Gao, X.; Stassinopoulos, A.; Goldberg, I. H. Biochemistry 1995, 34, 40-49.
7. 7) Myers, A. G.; Kort, M. E.; Hammond, M. J. Am. Chem. Soc. 1997, 119, 2965-2972.
8. 8) McDonald, L. A.; Capson, T. L.; Krishnamurthy, G. ; Ding, W.-D.; Ellestad, G. A.; Bernan, V. S.; Maiese, W. M.; Lassota, P.; Discafani, C.; Kramer, R. A.; Ireland, C. M. J. Am. Chem. Soc. 1996, 118, 10898-10899.