DNA binding agents

Non-DNA-binding agents include the vinca alkaloids and etoposide. These agents tend to cause injury in the pattern of a thermal burn and are cleared more easily from interstitial spaces. Thus they are more readily neutralized and tend to have a better healing prognosis. 

Bohl-Kullberg E, et al. Development of EGF-conjugated liposomes for targeted delivery of boronated DNA-binding agents. Bioconjugate Chem 2002 13 737. 

Figure 8.15 Schematic representation of resin-bound dynamic combinatorial chemistry and structures of the family of intercalating DNA binding agents M, [54],...

Lambert and co-workers49 (University of Melbourne) synthesized a library of cyclic thioether peptides with a pendant 9-aminoacridine moiety as a DNA-binding agent 81. Diversity in the library was achieved by assembling every permutation of four amino acid residues within the cyclic peptide (Scheme 24). The linear peptides 80 were synthesized in parallel with standard Fmoc chemistry on SynPhase Crowns functionalized with a Rink linker. The acridine moiety was incorporated onto the C-terminal lysine side chain using 9-phenoxyacridine. Cysteine deprotection and peptide cy-clization also took place under the acidic conditions used for the cleavage of 80 from the solid support. The library of cyclic thioether peptides 81 was obtained in high yields and purity (11 of 12 members had purities >95%). 

Scheme 24. Synthesis of acridinyl cyclic peptides as potential DNA-binding agents.

Fig. 1. Structures of dinuclear and trinuclear compounds containing the cisplatin synthon (2,2lc,c and 2,2,2tc,c,c) and the principal bifunctional DNA-binding agents studied. Abbreviations refer to the number of chloride leaving groups on each platinum and their geometry relative to the diamine bridge [22],...

Pretazettine (4), in combination with alkylating and DNA-binding agents, has been shown to have an increased beneficial effect in the treatment of certain malignant tumours. ... 

Hiruki, C. and Rocha, A.D.A. (1986). Hystochemical diagnosis of mycoplasma infections in Catharanthus roseus by means of a fluorescent DNA-binding agent, 4 -6 -diamidino-2-phenylindole-2 HC1 (DAPI). Canadian Journal of Plant Pathology, 8 185-188. 

AQ4N (23) is a prodrug of the DNA binding agent and topoisomerase inhibitor AQ4 (23a). The less toxic prodrug is activated in hypoxic tissue through reduction of the iV-oxide (Scheme ll).46,47... 

Reaction of 5-substituted isatoic anhydride with allylamines gave 2-amino-5-substituted-jV-alkyl-A -(2-propenyl)benzamides which were subjected to diazotization followed by subsequent nucleophilic substitution and cyclization to give 2-methyl-l,4-benzodiazepin-5-ones. A non-covalent DNA-binding agent like pyrrolo[2,l-c][l,4]benzodiazepine-5,ll-dione has been synthesized. 

Edited by Carole A. Bewley, National Institutes of Health, Bethesda, Maryland, USA Sequence-Specific DNA Binding Agents... 

Hydrazinopyridazine P-blocker Prizidilol Netropsin DNA binding agent... 

The noncovalent DNA-binding agents pyrrolo[2,l-c][l,4]benzodiazepine-5,ll-di-ones 769 have been successfully synthesized in 80-92% yields from isatoic anhydride... 

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