Spectroscopic and calorimetric studies on the DNA recognition of pyrrolo[2,1-c][1,4]benzodiazepine hybrids

被引：14
作者：
Rettig, Michael [1 ]
Kamal, Ahmed [2 ]
Ramu, R. [2 ]
Mikolajczak, Judith [1 ]
Weisz, Klaus [1 ]
机构：
[1] Ernst Moritz Arndt Univ Greifswald, Inst Biochem, D-17487 Greifswald, Germany
[2] Indian Inst Chem Technol, Div Organ Chem, Hyderabad 500007, Andhra Pradesh, India
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 02期
关键词：
Calorimetry; DNA recognition; Pyrrolobenzodiazepine; Spectroscopy; CROSS-LINKING AGENT; MINOR-GROOVE; HOECHST; 33258; DEOXYRIBONUCLEIC-ACID; BINDING AFFINITY; BIOLOGICAL EVALUATION; SEQUENCE SPECIFICITY; BIS-BENZIMIDAZOLE; MASS-SPECTROMETRY; ANTHRAMYCIN;
D O I：
10.1016/j.bmc.2008.11.033
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
DNA binding of two hybrid ligands composed of an alkylating pyrrolo[2,1-c][1,4] benzodiazepine (PBD) moiety tethered to either a naphthalimide or a phenyl benzimidazole chromophore was studied by DNA melting experiments, UV and fluorescence titrations, CD spectroscopy and isothermal titration calorimetry (ITC). Binding of both hybrids results in a remarkable thermal stabilization with an increase of DNA melting temperatures by up to 40 degrees C for duplexes that allow for a covalent attachment of the PBD moiety to guanine bases in their minor groove. CD spectroscopic measurements suggest that the naphthalimide moiety of the drug interacts through intercalation. In contrast, the PBD-benzimidazole hybrid binds in the DNA minor groove with a preference for (A, T)(4)G sequences. Whereas the binding of both ligands is enthalpy-driven and associated with a negative entropy, the benzimidazole hybrid exhibits a less favourable binding enthalpy that is counterbalanced by a more favourable entropic term when compared to the naphthalimide hybrid. (C) 2008 Elsevier Ltd. All rights reserved.
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收藏
页码：919 / 928
页数：10
相关论文
共 47 条
[1]   Chromophore-modified bisnaphthalimides:: DNA recognition, topoisomerase inhibition, and cytotoxic properties of two mono- and bisfuronaphthalimides [J].
Bailly, C ;
Carrasco, C ;
Joubert, A ;
Bal, C ;
Wattez, N ;
Hildebrand, MP ;
Lansiaux, A ;
Colson, P ;
Houssier, C ;
Cacho, M ;
Ramos, A ;
Braña, MF .
BIOCHEMISTRY, 2003, 42 (14) :4136-4150
[2]   Design, synthesis and biological activity of a pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-distamycin hybrid [J].
Baraldi, PG ;
Cacciari, B ;
Guiotto, A ;
Leoni, A ;
Romagnoli, R ;
Spalluto, G ;
Mongelli, N ;
Howard, PW ;
Thurston, DE ;
Bianchi, N ;
Gambari, R .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (21) :3019-3024
[3]   RATIONAL DESIGN OF A HIGHLY EFFICIENT IRREVERSIBLE DNA INTERSTRAND CROSS-LINKING AGENT BASED ON THE PYRROLOBENZODIAZEPINE RING-SYSTEM [J].
BOSE, DS ;
THOMPSON, AS ;
CHING, JS ;
HARTLEY, JA ;
BERARDINI, MD ;
JENKINS, TC ;
NEIDLE, S ;
HURLEY, LH ;
THURSTON, DE .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1992, 114 (12) :4939-4941
[4]   DNA minor groove recognition by bis-benzimidazole analogues of Hoechst 33258:: insights into structure-DNA affinity relationships assessed by fluorescence titration measurements [J].
Bostock-Smith, CE ;
Searle, MS .
NUCLEIC ACIDS RESEARCH, 1999, 27 (07) :1619-1624
[5]  
Chaires JB, 1997, BIOPOLYMERS, V44, P201, DOI 10.1002/(SICI)1097-0282(1997)44:3<201::AID-BIP2>3.0.CO
[6]  
2-Z
[7]   A thermodynamic signature for drug-DNA binding mode [J].
Chaires, Jonathan B. .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2006, 453 (01) :26-31
[8]   Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors [J].
David-Cordonnier, Marie-Helene ;
Hildebrand, Marie-Paule ;
Baldeyrou, Brigitte ;
Lansiaux, Amelie ;
Keuser, Christoph ;
Benzschawel, Kerstin ;
Lemster, Thomas ;
Pindur, Ulf .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2007, 42 (06) :752-771
[9]   DESIGN OF SEQUENCE-SPECIFIC DNA-BINDING MOLECULES [J].
DERVAN, PB .
SCIENCE, 1986, 232 (4749) :464-471
[10]  
Eftink MR, 1997, METHOD ENZYMOL, V278, P221
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