Abstract
Several DNA interacting agents of diverse chemical structure are among the most clinically useful antineoplastic drugs. Although they are also toxic to normal tissues, they possess some degree of selectivity and specificity against a variety of human tumours. There are tumours which are particularly sensitive to DNA-interacting agents (e.g. testicular tumours are often curable with cis-platin), but the reasons for this peculiar sensitivity are still unclear. A better understanding of the molecular basis of the sensitivity to such agents is necessary before any attempt can be made to design molecules which are more selective for different types of human neoplasms.
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References
Royer-Pokora B, Gordon LK and Haseltine WA: Use of exonuclease III to determine the site of stable lesions in defined sequences of DNA: the cyclobutane pyrimidine dimer and cis and trans dichlorodiammine platinum II examples. Nucleic Acids Res 1981 (9): 4595–4609
Ponti M, Forrow SM, Souhami RL, D’lncalci M and Hartley JA: Measurement of the sequence specificity of covalent DNA modification by antineoplastic agents using Taq DNA polymerase. Nucleic Acids Res 1991 (19): 2929–2933
Drew HR: Structural specificities of five commonly used DNA nucleases. J Molec Biology 1984 (176): 535–557
Dervan PB: Design of sequence-specific DNA-binding molecules. Science 1986 (232): 464–471
Raynolds VL, Molineux LJ, Kaplan D, Swenson DH and Hurley LH: Reaction of the antitumour antibiotic CC-1065 with DNA, location at the site of thermally induced strand breakage and analysis of DNA sequence specificity. Biochemistry 1985 (24): 6228–6237
Mattes WB, Harley JA and Kohn KW: DNA sequence selectivity of guanine N7 alkylation by nitrogen mustards. Nucleic Acids Res 1986 (14): 2971–2987
Hartley JA, Gibson NW, Kohn KW and Mattes WB: DNA sequence selectivity of guanine-N7 alkylation by three antitumour chlorethylating agents. Cancer Res 1986 (46): 1943–1947
Gibson NW, Mattes WB and Hartley JA: Identification of specific DNA lesions induced by three classes of chloroethylating agents: chloroethylnitrosoureas, chloroethylmethanesulfonates and chloroethylimi-dazotetrazines. Pharmac Ther 1985 (31): 153–163
Pullman A and Pullman B: Molecular electrostatic potential of the nucleic acids. Q Rev Biophys 1981 (14):289–380
Kohn KW, Hartley JA and Mattes WB: Mechanisms of DNA seuqence selective alkylation of guanine-N7 positions by nitrogen mustards. Nucl Acids Res 1987(14):10531–10549
Broggini M, Hartley JA, Mattes WB, Ponti M, Kohn KW and D’lncalci M: DNA damage and sequence selectivity of DNA binding of the new anticancer agent 1,4-bis(2-Chloroethyl)-1,4-diazabicyclo-[2.2. 1] heptane dimaleate. Br J Cancer 1990 (61): 285–289
Hartley JA, Berardini MD, Ponti M, Gibson NW, Thompson AS, Thurston DG, Hoey GM and Butler J: DNA crosslinking and sequence selectivity of aziridinylbenzoquinones: a unique reaction at 5′-GC-3′ sequences with 3,6-diaziridinyI-1,4-benzoquinone upon reduction. Biochem 1991 (30): 11719–11724
Sunters A, Springer CJ, Coombes RC, Bagshawe K, Souhami RL and Hartley JA: A comparison between the cytotoxicity, DNA crosslinking ability, and DNA sequence selectivity of the aniline mustard derivatives melphalan, chlorambucil, and para-N-2(chloro-ethyl)benzoic acid. Biochem Pharmacol 1992(41): in press
Hartley JA, Berardini MD and Souhami RL: An agarose gel method for the determination of DNA interstrand crosslinking applicable to the measurement of the rate of total and “second-arm” crosslink reactions. Analyt Biochem 1991 (193): 131–134
Borowy-Borowsky H, Lipman R, Chowdary D and Tomasz M: Recognition between mitomycin C and specific DNA sequences for crosslink formation. Biochemistry 1990 (29): 2999–3006
Hurley LH, Warpehoski MA, Lee CS, McGovern JP, Scahill TA, Kelly KC, Wicnieski NA, Gebhard I and Bradford VS: Sequence specificity of DNA alkylation by the unnatural enantiomers of CC-1065 and its synthetic analogs. J Am Chem Soc 1990 (112):4633–4649
Li LH, Wallace TL, DeKoning TF, Warpehoski MA, Kelly RC, Priairie MD and Krueger WC: Structure and activity relationship of several novel CC-1065 analogs. Invest New Drugs 1987 (5): 329–337
Arcamone FM, Animati F, Barbieri B, Configliacchi E, D’Alessio R, Geroni C, Giuliani FC, Lazzari E, Menozzi M, Mongelli N, Penco S and Verini MA: Synthesis, DNA-binding properties, and antitumor activity of novel distamycin derivative. J Med Chem 1989 (32):774–778
Broggini M, Erba E, Ponti M, Ballinari D, Geroni C, Spreafico F and D’lncalci M: Selective DNA interaction of the novel distamycin derivative FCE 24517. Cancer Res 1991 (51): 199–204
Bose DS, Thompson AS, Ching J, Hartley JA, Berardini MD, Jenkins TC, Neidle S, Hurley LH and Thurston DE: Rational design of a highly efficient irreversible DNA interstrand cross-linking agent based on the pyrrolobenzodiazepine ring system. J Am Chem Soc 1992 (114): 4939–4941
Broggini M, Ponti M, Ottolenghi S, D’lnalci M, Mongelli N and Mantovani R: Distamycins inhibit the binding of OTF-1 and NFE-1 transfactors to their conserved DNA elements. Nucleic Acids Res 1989 (17):1051–1059
Dorn A, Affolter M, Müller M, Gehring WJ and Leupin W: Distamycin-induced inhibition of homeodomain-DNA complexes. EMBO J 1992 (11): 279–286
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© 1992 Springer-Verlag Berlin Heidelberg
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D’lncalci, M., Broggini, M., Hartley, J.A. (1992). Sequence and Gene-Specific Drugs. In: Workman, P. (eds) New Approaches in Cancer Pharmacology: Drug Design and Development. ESO Monographs. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77874-2_2
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DOI: https://doi.org/10.1007/978-3-642-77874-2_2
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