DNA-binding properties of a distamycin-ellipticine hybrid molecule

We have synthesized a distamycin-ellipticine hybrid compound and investigated its interaction with DNA, using various optical and gel electrophoresis techniques. Binding of the hybrid to DNA is evidenced by spectral shifts, fluorescence quenching, and induced linear dichroism. Absorbance measurement...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular pharmacology 1992-05, Vol.41 (5), p.845-855
Hauptverfasser: Bailly, C, O'Huigin, C, Houssin, R, Colson, P, Houssier, C, Rivalle, C, Bisagni, E, Henichart, J P, Waring, M J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page 855
container_issue 5
container_start_page 845
container_title Molecular pharmacology
container_volume 41
creator Bailly, C
O'Huigin, C
Houssin, R
Colson, P
Houssier, C
Rivalle, C
Bisagni, E
Henichart, J P
Waring, M J
description We have synthesized a distamycin-ellipticine hybrid compound and investigated its interaction with DNA, using various optical and gel electrophoresis techniques. Binding of the hybrid to DNA is evidenced by spectral shifts, fluorescence quenching, and induced linear dichroism. Absorbance measurements have been used to generate Scatchard plots, which reveal that the interaction cannot be described adequately in terms of a single binding mode, probably because of simultaneous intercalation and minor groove binding of the ligand. Competition with added distamycin has been used to verify involvement of the N-methyl-pyrrole portion of the hybrid molecule in the binding reaction. From electric linear dichroism experiments, it is estimated that the orientation of the DNA-bound ellipticine chromophore in the hybrid differs by about 10 degrees from the orientation of the equivalent chromophore lacking a distamycin tail. Topoisomerase assays establish that binding of the hybrid unwinds the DNA helix by a minimum of 11 degrees, which is consistent with intercalation but notably smaller than the unwinding angle of ellipticine. In footprinting experiments, it is found that the AT- and GC-specificity of distamycin and ellipticine, respectively, appear to be merged in the binding of the hybrid, which produces a pattern of protection distinct from the characteristic patterns for either of the parent compounds. The hybrid is an extremely effective inhibitor of cutting by DNase I.
doi_str_mv 10.1016/S0026-895X(25)09129-1
format Article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_72952226</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0026895X25091291</els_id><sourcerecordid>72952226</sourcerecordid><originalsourceid>FETCH-LOGICAL-c367t-fd6c225f87d9080e407ee728ac0f5fe7c9741160360c49f4fc38387654fe5ba03</originalsourceid><addsrcrecordid>eNqFkE1v1DAQhi1EVZbCT6iUAyA4BGacOLZPqBRokSo4ABI3y-uMd43yVTtbtP8eb7MqR04eaZ53_Oph7BzhLQI2774D8KZUWvx6zcUb0Mh1iY_YCgXHEhDxMVs9IE_Y05R-A2AtFJyyUxRKadQr9uHj14tyHYY2DJtiiuNEcQ6UitEXtmhDmm2_d2EoqevCNIc8UrHdr2Noi37syO06esZOvO0SPT--Z-zn508_Lq_Lm29XXy4vbkpXNXIufds4zoVXstWggGqQRJIr68ALT9JpWSM2UDXgau1r7ypVKdmI2pNYW6jO2Kvlbq55u6M0mz4kl4vZgcZdMpJrwTlvMigW0MUxpUjeTDH0Nu4Ngjm4M_fuzEGM4cLcuzOYc-fHD3brntp_qUVW3r847m1ytvPRDi6kB0xwVUl5wF4u2DZstn9CJDNtbeytG7txszc1GmFULTL3fuEoS7sLFE1ygQZHbc642bRj-E_hv_UGl9M</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>72952226</pqid></control><display><type>article</type><title>DNA-binding properties of a distamycin-ellipticine hybrid molecule</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Bailly, C ; O'Huigin, C ; Houssin, R ; Colson, P ; Houssier, C ; Rivalle, C ; Bisagni, E ; Henichart, J P ; Waring, M J</creator><creatorcontrib>Bailly, C ; O'Huigin, C ; Houssin, R ; Colson, P ; Houssier, C ; Rivalle, C ; Bisagni, E ; Henichart, J P ; Waring, M J</creatorcontrib><description>We have synthesized a distamycin-ellipticine hybrid compound and investigated its interaction with DNA, using various optical and gel electrophoresis techniques. Binding of the hybrid to DNA is evidenced by spectral shifts, fluorescence quenching, and induced linear dichroism. Absorbance measurements have been used to generate Scatchard plots, which reveal that the interaction cannot be described adequately in terms of a single binding mode, probably because of simultaneous intercalation and minor groove binding of the ligand. Competition with added distamycin has been used to verify involvement of the N-methyl-pyrrole portion of the hybrid molecule in the binding reaction. From electric linear dichroism experiments, it is estimated that the orientation of the DNA-bound ellipticine chromophore in the hybrid differs by about 10 degrees from the orientation of the equivalent chromophore lacking a distamycin tail. Topoisomerase assays establish that binding of the hybrid unwinds the DNA helix by a minimum of 11 degrees, which is consistent with intercalation but notably smaller than the unwinding angle of ellipticine. In footprinting experiments, it is found that the AT- and GC-specificity of distamycin and ellipticine, respectively, appear to be merged in the binding of the hybrid, which produces a pattern of protection distinct from the characteristic patterns for either of the parent compounds. The hybrid is an extremely effective inhibitor of cutting by DNase I.</description><identifier>ISSN: 0026-895X</identifier><identifier>EISSN: 1521-0111</identifier><identifier>DOI: 10.1016/S0026-895X(25)09129-1</identifier><identifier>PMID: 1588919</identifier><identifier>CODEN: MOPMA3</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Antineoplastic agents ; Biological and medical sciences ; Chelating Agents - chemistry ; Distamycins - chemistry ; DNA - chemistry ; Ellipticines - chemistry ; General aspects ; Medical sciences ; Nucleic Acid Conformation ; Nucleic Acid Denaturation ; Pharmacology. Drug treatments ; Poly dA-dT - chemistry ; Spectrometry, Fluorescence ; Spectrophotometry ; Thermodynamics</subject><ispartof>Molecular pharmacology, 1992-05, Vol.41 (5), p.845-855</ispartof><rights>1992 American Society for Pharmacology and Experimental Therapeutics</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=5283779$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1588919$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bailly, C</creatorcontrib><creatorcontrib>O'Huigin, C</creatorcontrib><creatorcontrib>Houssin, R</creatorcontrib><creatorcontrib>Colson, P</creatorcontrib><creatorcontrib>Houssier, C</creatorcontrib><creatorcontrib>Rivalle, C</creatorcontrib><creatorcontrib>Bisagni, E</creatorcontrib><creatorcontrib>Henichart, J P</creatorcontrib><creatorcontrib>Waring, M J</creatorcontrib><title>DNA-binding properties of a distamycin-ellipticine hybrid molecule</title><title>Molecular pharmacology</title><addtitle>Mol Pharmacol</addtitle><description>We have synthesized a distamycin-ellipticine hybrid compound and investigated its interaction with DNA, using various optical and gel electrophoresis techniques. Binding of the hybrid to DNA is evidenced by spectral shifts, fluorescence quenching, and induced linear dichroism. Absorbance measurements have been used to generate Scatchard plots, which reveal that the interaction cannot be described adequately in terms of a single binding mode, probably because of simultaneous intercalation and minor groove binding of the ligand. Competition with added distamycin has been used to verify involvement of the N-methyl-pyrrole portion of the hybrid molecule in the binding reaction. From electric linear dichroism experiments, it is estimated that the orientation of the DNA-bound ellipticine chromophore in the hybrid differs by about 10 degrees from the orientation of the equivalent chromophore lacking a distamycin tail. Topoisomerase assays establish that binding of the hybrid unwinds the DNA helix by a minimum of 11 degrees, which is consistent with intercalation but notably smaller than the unwinding angle of ellipticine. In footprinting experiments, it is found that the AT- and GC-specificity of distamycin and ellipticine, respectively, appear to be merged in the binding of the hybrid, which produces a pattern of protection distinct from the characteristic patterns for either of the parent compounds. The hybrid is an extremely effective inhibitor of cutting by DNase I.</description><subject>Antineoplastic agents</subject><subject>Biological and medical sciences</subject><subject>Chelating Agents - chemistry</subject><subject>Distamycins - chemistry</subject><subject>DNA - chemistry</subject><subject>Ellipticines - chemistry</subject><subject>General aspects</subject><subject>Medical sciences</subject><subject>Nucleic Acid Conformation</subject><subject>Nucleic Acid Denaturation</subject><subject>Pharmacology. Drug treatments</subject><subject>Poly dA-dT - chemistry</subject><subject>Spectrometry, Fluorescence</subject><subject>Spectrophotometry</subject><subject>Thermodynamics</subject><issn>0026-895X</issn><issn>1521-0111</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1v1DAQhi1EVZbCT6iUAyA4BGacOLZPqBRokSo4ABI3y-uMd43yVTtbtP8eb7MqR04eaZ53_Oph7BzhLQI2774D8KZUWvx6zcUb0Mh1iY_YCgXHEhDxMVs9IE_Y05R-A2AtFJyyUxRKadQr9uHj14tyHYY2DJtiiuNEcQ6UitEXtmhDmm2_d2EoqevCNIc8UrHdr2Noi37syO06esZOvO0SPT--Z-zn508_Lq_Lm29XXy4vbkpXNXIufds4zoVXstWggGqQRJIr68ALT9JpWSM2UDXgau1r7ypVKdmI2pNYW6jO2Kvlbq55u6M0mz4kl4vZgcZdMpJrwTlvMigW0MUxpUjeTDH0Nu4Ngjm4M_fuzEGM4cLcuzOYc-fHD3brntp_qUVW3r847m1ytvPRDi6kB0xwVUl5wF4u2DZstn9CJDNtbeytG7txszc1GmFULTL3fuEoS7sLFE1ygQZHbc642bRj-E_hv_UGl9M</recordid><startdate>19920501</startdate><enddate>19920501</enddate><creator>Bailly, C</creator><creator>O'Huigin, C</creator><creator>Houssin, R</creator><creator>Colson, P</creator><creator>Houssier, C</creator><creator>Rivalle, C</creator><creator>Bisagni, E</creator><creator>Henichart, J P</creator><creator>Waring, M J</creator><general>Elsevier Inc</general><general>American Society for Pharmacology and Experimental Therapeutics</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19920501</creationdate><title>DNA-binding properties of a distamycin-ellipticine hybrid molecule</title><author>Bailly, C ; O'Huigin, C ; Houssin, R ; Colson, P ; Houssier, C ; Rivalle, C ; Bisagni, E ; Henichart, J P ; Waring, M J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c367t-fd6c225f87d9080e407ee728ac0f5fe7c9741160360c49f4fc38387654fe5ba03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>Antineoplastic agents</topic><topic>Biological and medical sciences</topic><topic>Chelating Agents - chemistry</topic><topic>Distamycins - chemistry</topic><topic>DNA - chemistry</topic><topic>Ellipticines - chemistry</topic><topic>General aspects</topic><topic>Medical sciences</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleic Acid Denaturation</topic><topic>Pharmacology. Drug treatments</topic><topic>Poly dA-dT - chemistry</topic><topic>Spectrometry, Fluorescence</topic><topic>Spectrophotometry</topic><topic>Thermodynamics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bailly, C</creatorcontrib><creatorcontrib>O'Huigin, C</creatorcontrib><creatorcontrib>Houssin, R</creatorcontrib><creatorcontrib>Colson, P</creatorcontrib><creatorcontrib>Houssier, C</creatorcontrib><creatorcontrib>Rivalle, C</creatorcontrib><creatorcontrib>Bisagni, E</creatorcontrib><creatorcontrib>Henichart, J P</creatorcontrib><creatorcontrib>Waring, M J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bailly, C</au><au>O'Huigin, C</au><au>Houssin, R</au><au>Colson, P</au><au>Houssier, C</au><au>Rivalle, C</au><au>Bisagni, E</au><au>Henichart, J P</au><au>Waring, M J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA-binding properties of a distamycin-ellipticine hybrid molecule</atitle><jtitle>Molecular pharmacology</jtitle><addtitle>Mol Pharmacol</addtitle><date>1992-05-01</date><risdate>1992</risdate><volume>41</volume><issue>5</issue><spage>845</spage><epage>855</epage><pages>845-855</pages><issn>0026-895X</issn><eissn>1521-0111</eissn><coden>MOPMA3</coden><abstract>We have synthesized a distamycin-ellipticine hybrid compound and investigated its interaction with DNA, using various optical and gel electrophoresis techniques. Binding of the hybrid to DNA is evidenced by spectral shifts, fluorescence quenching, and induced linear dichroism. Absorbance measurements have been used to generate Scatchard plots, which reveal that the interaction cannot be described adequately in terms of a single binding mode, probably because of simultaneous intercalation and minor groove binding of the ligand. Competition with added distamycin has been used to verify involvement of the N-methyl-pyrrole portion of the hybrid molecule in the binding reaction. From electric linear dichroism experiments, it is estimated that the orientation of the DNA-bound ellipticine chromophore in the hybrid differs by about 10 degrees from the orientation of the equivalent chromophore lacking a distamycin tail. Topoisomerase assays establish that binding of the hybrid unwinds the DNA helix by a minimum of 11 degrees, which is consistent with intercalation but notably smaller than the unwinding angle of ellipticine. In footprinting experiments, it is found that the AT- and GC-specificity of distamycin and ellipticine, respectively, appear to be merged in the binding of the hybrid, which produces a pattern of protection distinct from the characteristic patterns for either of the parent compounds. The hybrid is an extremely effective inhibitor of cutting by DNase I.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>1588919</pmid><doi>10.1016/S0026-895X(25)09129-1</doi><tpages>11</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0026-895X
ispartof Molecular pharmacology, 1992-05, Vol.41 (5), p.845-855
issn 0026-895X
1521-0111
language eng
recordid cdi_proquest_miscellaneous_72952226
source MEDLINE; EZB-FREE-00999 freely available EZB journals
subjects Antineoplastic agents
Biological and medical sciences
Chelating Agents - chemistry
Distamycins - chemistry
DNA - chemistry
Ellipticines - chemistry
General aspects
Medical sciences
Nucleic Acid Conformation
Nucleic Acid Denaturation
Pharmacology. Drug treatments
Poly dA-dT - chemistry
Spectrometry, Fluorescence
Spectrophotometry
Thermodynamics
title DNA-binding properties of a distamycin-ellipticine hybrid molecule
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T14%3A21%3A06IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA-binding%20properties%20of%20a%20distamycin-ellipticine%20hybrid%20molecule&rft.jtitle=Molecular%20pharmacology&rft.au=Bailly,%20C&rft.date=1992-05-01&rft.volume=41&rft.issue=5&rft.spage=845&rft.epage=855&rft.pages=845-855&rft.issn=0026-895X&rft.eissn=1521-0111&rft.coden=MOPMA3&rft_id=info:doi/10.1016/S0026-895X(25)09129-1&rft_dat=%3Cproquest_cross%3E72952226%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=72952226&rft_id=info:pmid/1588919&rft_els_id=S0026895X25091291&rfr_iscdi=true