Modulation of topoisomerase IIα expression by a DNA sequence-specific polyamide (2007)
Hochhauser, D., Kotecha, M., O'Hare, C., Morris, P.J., Hartley, J.M., Taherbhai, Z., ...
Topoisomerase II (topo II) is an important target for several chemotherapeutic agents, including etoposide and doxorubicin. Confluent cells express low levels of topo II and are resistant to...
Mayer, A., Francis, R.J., Sharma, S.K., Tolner, B., Springer, C.J., Martin, J., ...
Purpose: Antibody-directed enzyme prodrug therapy is a two-stage treatment whereby a tumor-targeted antibody-enzyme complex localizes in tumor for selective conversion of prodrug. The purpose of this...
Friedmann, B.J., Caplin, M., Savic, B., Shah, T., Lord, C.J., Ashworth, A., ...
The epidermal growth factor receptor (EGFR) is an important target for cancer therapy. We previously showed that the EGFR inhibitor gefitinib modulated repair of DNA damage following exposure to...
Clingen, P.H., De Silva, I.U., McHugh, P.J., Ghadessy, F.J., Tilby, M.J., Thurston, D.E., ...
SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136...
Clingen, P.H., De Silva, I.U., McHugh, P.J., Ghadessy, F.J., Tilby, M.J., Thurston, D.E., ...
SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136...
Friedmann, B., Caplin, M., Hartley, J.A., Hochhauser, D.
Purpose: The epidermal growth factor receptor (EGFR) is commonly expressed in human tumors and provides a target for therapy. Gefitinib (Iressa, ZD1839) is a quinazoline derivative that inhibits EGFR...
Hartley, J.A., Spanswick, V.J., Brooks, N., Clingen, P.H., McHugh, P.J., Hochhauser, D., ...
SJG-136 (NSC 694501) is a rationally designed pyrrolobenzodiazepine dimer that binds in the minor groove of DNA. It spans 6 bp with a preference for binding to purine-GATC-pyrimidine sequences. The...
Design and synthesis of a nitrogen mustard derivative stabilized by apo-neocarzinostatin (2004)
Urbaniak, M.D., Bingham, J.P., Hartley, J.A., Woolfson, D.N., Caddick, S.
Neocarzinostatin (NCS) is an antitumor antibiotic comprising a 1:1 protein-chromophore complex and exhibits cytotoxic action through DNA cleavage via H-abstraction. Cytotoxic activity resides with...
Spanswick, V.J., Craddock, C., Sekhar, M., Mahendra, P., Shankaranarayana, P., Hughes, R.G., ...
Melphalan is widely used as a preparative agent in patients with multiple myeloma (MM) undergoing autologous stem cell transplantation (SCT). Although disease relapse is the major cause of death...
O'Hare, C.C., Mack, D., Tandon, M., Sharma, S.K., Lown, J.W., Kopka, M.L., ...
Development of sequence-reading polyamides or "lexitropsins" with comparable DNA-binding affinities to cellular proteins raises the possibility of artificially regulated gene expression. Covalent...
Tolner, B., Hartley, J.A., Hochhauser, D.
Topoisomerase II is a critical gene involved in DNA replication and maintenance of genomic stability. Several chemotherapeutic agents target topoisomerase II and levels of expression are an important...
Wyatt, M D, Lee, M, Hartley, J A
The covalent sequence specificity of a series of nitrogen mustard and imidazole-containing analogues of distamycin was determined using modified sequencing techniques. The analogues tether benzoic...
Sunters, A, Grimaldi, K A, Souhami, R L, Hartley, J A
The levels of N-alkyl purine and DNA interstrand crosslink formation, produced by the clinically used nitrogen mustard antitumour drug mechlorethamine (HN2), were quantitated at the level of specific...
Excision repair of nitrogen mustard-DNA adducts in Saccharomyces cerevisiae.
McHugh, P J, Gill, R D, Waters, R, Hartley, J A
The bifunctional alkylating anticancer drug nitrogen mustard forms a variety of DNA lesions, including monoadducts and intrastrand and interstrand crosslinks. Although it is known that nucleotide...
Morvan, F, Rayner, B, Imbach, J L, Lee, M, Hartley, J A, Chang, D K, ...
The beta-complementary hexamer, beta-d[GTACGC], to the alpha-sequence, alpha-d[CATGCG], was synthesized by the phosphotriester method. The non-exchangeable proton assignments were obtained using 1D-...
Broggini, M, Coley, H M, Mongelli, N, Pesenti, E, Wyatt, M D, Hartley, J A, ...
FCE 24517, a novel distamycin derivative possessing potent antitumor activity, is under initial clinical investigation in Europe. In spite of the presence of a benzoyl nitrogen mustard group this...
Puvvada, M S, Hartley, J A, Jenkins, T C, Thurston, D E
An assay has been developed (restriction endonuclease digestion assay--RED100) based on inhibition of the restriction endonuclease BamHI that is capable of quantitative evaluation of the relative...
Ponti, M, Forrow, S M, Souhami, R L, D'Incalci, M, Hartley, J A
A polymerase stop assay has been developed to determine the DNA nucleotide sequence specificity of covalent modification by antineoplastic agents using the thermostable DNA polymerase from Thermus...
Lee, M, Hartley, J A, Pon, R T, Krowicki, K, Lown, J W
All 1H-NMR resonances of d-[CATGGCCATG]2 and the 1:1 complex of lexitropsin 1 and the DNA were assigned by the NOE difference, COSY and NOESY methods. Addition of 1 causes the base and imino protons...
DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards.
Mattes, W B, Hartley, J A, Kohn, K W
Nitrogen mustards alkylate DNA primarily at the N7 position of guanine. Using an approach analogous to that of the Maxam-Gilbert procedure for DNA sequence analysis, we have examined the relative...
Mechanisms of DNA sequence selective alkylation of guanine-N7 positions by nitrogen mustards.
Kohn, K W, Hartley, J A, Mattes, W B
Quantitative determinations were carried out of the relative reaction rates of several nitrogen mustards at various guanine-N7 positions in DNA fragments of known sequence. The findings suggest...
Grimaldi, K A, McAdam, S R, Souhami, R L, Hartley, J A
A new PCR based technique has been developed to investigate the sequence selectivity of adduct formation by DNA damaging agents in a single copy gene in isolated genomic DNA or in drug treated cells....
DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards is preserved in intact cells.
Hartley, J A, Bingham, J P, Souhami, R L
Nitrogen mustard alkylating agents react with isolated DNA in a sequence selective manner, and the substituent attached to the drug reactive group can impose a distinct sequence preference. It is not...
Wyatt, M D, Lee, M, Hartley, J A
The covalent sequence specificity of a series of nitrogen mustard and imidazole-containing analogues of distamycin was determined using modified sequencing techniques. The analogues tether benzoic...
Sunters, A, Grimaldi, K A, Souhami, R L, Hartley, J A
The levels of N-alkyl purine and DNA interstrand crosslink formation, produced by the clinically used nitrogen mustard antitumour drug mechlorethamine (HN2), were quantitated at the level of specific...
Excision repair of nitrogen mustard-DNA adducts in Saccharomyces cerevisiae.
McHugh, P J, Gill, R D, Waters, R, Hartley, J A
The bifunctional alkylating anticancer drug nitrogen mustard forms a variety of DNA lesions, including monoadducts and intrastrand and interstrand crosslinks. Although it is known that nucleotide...
Morvan, F, Rayner, B, Imbach, J L, Lee, M, Hartley, J A, Chang, D K, ...
The beta-complementary hexamer, beta-d[GTACGC], to the alpha-sequence, alpha-d[CATGCG], was synthesized by the phosphotriester method. The non-exchangeable proton assignments were obtained using 1D-...
Broggini, M, Coley, H M, Mongelli, N, Pesenti, E, Wyatt, M D, Hartley, J A, ...
FCE 24517, a novel distamycin derivative possessing potent antitumor activity, is under initial clinical investigation in Europe. In spite of the presence of a benzoyl nitrogen mustard group this...
Puvvada, M S, Hartley, J A, Jenkins, T C, Thurston, D E
An assay has been developed (restriction endonuclease digestion assay--RED100) based on inhibition of the restriction endonuclease BamHI that is capable of quantitative evaluation of the relative...
DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards is preserved in intact cells.
Hartley, J A, Bingham, J P, Souhami, R L
Nitrogen mustard alkylating agents react with isolated DNA in a sequence selective manner, and the substituent attached to the drug reactive group can impose a distinct sequence preference. It is not...
Ponti, M, Forrow, S M, Souhami, R L, D'Incalci, M, Hartley, J A
A polymerase stop assay has been developed to determine the DNA nucleotide sequence specificity of covalent modification by antineoplastic agents using the thermostable DNA polymerase from Thermus...
Lee, M, Hartley, J A, Pon, R T, Krowicki, K, Lown, J W
All 1H-NMR resonances of d-[CATGGCCATG]2 and the 1:1 complex of lexitropsin 1 and the DNA were assigned by the NOE difference, COSY and NOESY methods. Addition of 1 causes the base and imino protons...
DNA sequence selectivity of guanine-N7 alkylation by nitrogen mustards.
Mattes, W B, Hartley, J A, Kohn, K W
Nitrogen mustards alkylate DNA primarily at the N7 position of guanine. Using an approach analogous to that of the Maxam-Gilbert procedure for DNA sequence analysis, we have examined the relative...
Mechanisms of DNA sequence selective alkylation of guanine-N7 positions by nitrogen mustards.
Kohn, K W, Hartley, J A, Mattes, W B
Quantitative determinations were carried out of the relative reaction rates of several nitrogen mustards at various guanine-N7 positions in DNA fragments of known sequence. The findings suggest...
Grimaldi, K A, McAdam, S R, Souhami, R L, Hartley, J A
A new PCR based technique has been developed to investigate the sequence selectivity of adduct formation by DNA damaging agents in a single copy gene in isolated genomic DNA or in drug treated cells....