- DNA alkylation by pyrrole-imidazole seco-CBI conjugates with an indole linker: Sequence-specific DNA alkylation with 10-base-pair recognition through heterodimer formation
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The sequence-specific DNA alkylation by conjugates 4 and 5, which consist of N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) linked with an indole linker, was investigated in the absence or presence of partner Py-Im polyamide 6. High-resolution denaturing Polyacrylamide gel electrophoresis revealed that conjugate 4 alkylates DNA at the sequences 5′-(A/T)GCCTA- 3′ through hairpin formation, and alkylates 5′-GGAAA-GAAAA-3′ through an extended binding mode. However, in the presence of partner Py-Im polyamide 6, conjugate 4 alkylates DNA at a completely different sequence, 5′-AGGTTGTCCA-3′. Alkylation of 4 in the presence of 6 was effectively inhibited by a competitor 7. Surface plasmon resonance (SPR) results indicated that conjugate 4 does not bind to 5′-AGGTTGTCCA-3′, whereas 6 binds tightly to this sequence. The results suggest that alkylation proceeds through heterodimer formation, indicating that this is a general way to expand the recognition sequence for DNA alkylation by Py-Im seco-CBI conjugates.
- Minoshima, Masafumi,Bando, Toshikazu,Sasaki, Shunta,Shinohara, Ken-Ichi,Shimizu, Tatsuhiko,Fujimoto, Jun,Sugiyama, Hiroshi
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- CHEMICAL LINKERS AND CLEAVABLE SUBSTRATES AND CONJUGATES THEREOF
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The present disclosure provides drug-ligand conjugates and drug-cleavable substrate conjugates that are potent cytotoxins. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.
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Page/Page column 62; 64
(2010/06/19)
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- CHEMICAL LINKERS WITH SINGLE AMINO ACIDS AND CONJUGATES THEREOF
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The present disclosure provides drug-ligand conjugates that are potent cytotoxins and include a linker between the drug and ligand where the linker has a single amino acid. The disclosure is also directed to compositions containing the drug-ligand conjugates, and to methods of treatment using them.
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- CHEMICAL COMPOUNDS
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The present invention relates to compounds that are a non-nucleoside reverse transcriptase inhibitors, and to processes for the preparation and use of the same. Specifically, the present invention includes methods of using such compounds in the treatment of human immunodeficiency virus infection.
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- Synthesis and preliminary cytotoxicity study of glucuronide derivatives of CC-1065 analogues
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Glucuronide derivatives of CBI-bearing CC-1065 analogues have been synthesized, and their cytotoxicities tested against U937 leukemia cells. The new compounds show potent antitumor activity in vitro. Compounds 1 and 2, and their corresponding glucuronides
- Wang, Yuqiang,Yuan, Huiling,Wright, Susan C.,Wang, Hong,Larrick, James W.
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p. 1569 - 1575
(2007/10/03)
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- Analogs of duocarmycin and cc-1065
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The field of this invention is antitumor antibiotics. More particularly, the present invention relates to analogs of duocarmycin and CC-1065, which analogs have antitumor antibiotics activity.
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The present invention relates to novel DNA alkylating agents and the prodrugs of these agents which are useful as antitumor agents and DNA labelling agents. The compounds are hydroxy dihydrobenzindole oligopeptides and prodrugs thereof wherein the monomeric constituents are derived from monocyclic or bicyclic heterocyclic aromatic residues.
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