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Synthesis of Metallointercalator−DNA Conjugates on a Solid Support

Holmlin, R. Erik and Dandliker, Peter J. and Barton, Jacqueline K. (1999) Synthesis of Metallointercalator−DNA Conjugates on a Solid Support. Bioconjugate Chemistry, 10 (6). pp. 1122-1130. ISSN 1043-1802. doi:10.1021/bc9900791.

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Metallointercalator−DNA conjugates were prepared by amide bond formation between active esters on the nonintercalating ligands of transition metal complexes and primary amines presented at the 5' or the 3' termini of oligonucleotides attached to solid supports. The conjugates were liberated from the support by aminolysis and purified by HPLC on C18 or C4 stationary phases, which separates the two diastereomeric forms of the conjugates containing either the Λ or the Δ enantiomer of the octahedral metal complex. The coupling reaction proceeds with ∼75% conversion of the amino-terminated oligonucleotide into the conjugate; the isolated yield is ∼200 nmol for syntheses initiated on DNA-synthesis columns with a loading of 2 μmol. The conjugates were characterized by ultraviolet−visible and circular dichorism absorption spectroscopy, electrospray ionization mass spectrometry, enzymatic digestion, and polyacrylamide gel electrophoresis (PAGE). Oligonucleotides bearing [Rh(phi)_2(bpy')]^(3+) (phi = 9,10-phenanthrene quinone diimine; bpy' = 4-butyric acid-4'-methyl bipyridyl) form 1:1 duplexes with the complementary strand, and the electrophoretic mobility under nondenaturating PAGE of duplexes containing Δ-Rh is notably different from duplexes containing Λ-Rh. High-resolution PAGE of DNA photocleavage reactions initiated by irradiation of the tethered Rh complexes reveal intercalation of the complex only near the tethered end of the duplex. Analogous DNA-binding properties were observed with [Rh(phi)_2(bpy')]^(3+) tethered to the 3' terminus. By combining the 3‘ and 5‘ modification strategies, a mixed-metal DNA conjugate containing both [Os(phen)(bpy')(Me_2-dppz)]^(2+) (Me_2-dppz = 7,8-dimethyldipyridophenazine) on the 3' terminus and [Rh(phi)_2(bpy')]^(3+) on the 5' terminus was prepared and isolated. Taken together, these strategies for preparing metallointercalator−DNA conjugates offer a useful approach to generate chemical assemblies to probe long-range DNA-mediated charge transfer where the redox initiator is confined to and intercalated in a well-defined binding site.

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Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 1999 American Chemical Society. Received 21 June 1999. Published online 21 October 1999. Published in print 1 November 1999. We are grateful to the NIH for their financial support. We also thank the Parsons Foundation (R.E.H.) and the Damon-Runyon Walter Winchell Cancer Fund (P.J.D.) for fellowship support.
Funding AgencyGrant Number
Ralph M. Parsons FoundationUNSPECIFIED
Damon-Runyon Walter Winchell Cancer FundUNSPECIFIED
Issue or Number:6
Record Number:CaltechAUTHORS:20180202-151812038
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Official Citation:Synthesis of Metallointercalator−DNA Conjugates on a Solid Support R. Erik Holmlin, Peter J. Dandliker, and Jacqueline K. Barton Bioconjugate Chemistry 1999 10 (6), 1122-1130 DOI: 10.1021/bc9900791
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84658
Deposited By: Ruth Sustaita
Deposited On:02 Feb 2018 23:32
Last Modified:15 Nov 2021 20:21

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