Competitive formation of both long-range 5'-5' and short-range antiparallel 3'- 3' DNA interstrand cross-links by a trinuclear platinum complex on binding to a 10-mer duplex

View/ Open
Author(s)
Ruhayel, Rasha A
Berners-Price, Susan J
Farrell, Nicholas P
Year published
2013
Metadata
Show full item recordAbstract
2D [1H, 15N] HSQC NMR spectroscopy has been used to monitor the reaction of fully 15N-labelled [{trans-PtCl(NH3)2}2(μ-trans-Pt(NH3)2{NH2(CH2)6NH2}2)]4+ (Triplatin, BBR3464 or 1,0,1/t,t,t (15N-1)) with the self-complementary 10-mer DNA duplex 5′-{d(ACGTATACGT)2} (duplex I) at pH 5.4 and 298 K. Initial electrostatic interactions were observed in the minor groove of the duplex, followed directly by aquation to form the monoaqua monochloro species. There was evidence for two discrete monofunctional adducts, through covalent binding at the guanine N7 sites, and one had distinctly different 1H/15N chemical shifts to those observed ...
View more >2D [1H, 15N] HSQC NMR spectroscopy has been used to monitor the reaction of fully 15N-labelled [{trans-PtCl(NH3)2}2(μ-trans-Pt(NH3)2{NH2(CH2)6NH2}2)]4+ (Triplatin, BBR3464 or 1,0,1/t,t,t (15N-1)) with the self-complementary 10-mer DNA duplex 5′-{d(ACGTATACGT)2} (duplex I) at pH 5.4 and 298 K. Initial electrostatic interactions were observed in the minor groove of the duplex, followed directly by aquation to form the monoaqua monochloro species. There was evidence for two discrete monofunctional adducts, through covalent binding at the guanine N7 sites, and one had distinctly different 1H/15N chemical shifts to those observed previously in analogous reactions. Bifunctional adduct formation followed by binding at a second guanine N7 site with evidence for both the 3′–3′ 1,2-GG and 5′–5′ 1,6-GG interstrand cross-links in a ratio of 2 : 1. The results show that cross-link preference is kinetically controlled and will depend critically on the reaction conditions, explaining why in a previous reaction of 1 with duplex I the major adduct isolated by HPLC had two simultaneous 3′–3′ 1,2-interstrand cross-links.
View less >
View more >2D [1H, 15N] HSQC NMR spectroscopy has been used to monitor the reaction of fully 15N-labelled [{trans-PtCl(NH3)2}2(μ-trans-Pt(NH3)2{NH2(CH2)6NH2}2)]4+ (Triplatin, BBR3464 or 1,0,1/t,t,t (15N-1)) with the self-complementary 10-mer DNA duplex 5′-{d(ACGTATACGT)2} (duplex I) at pH 5.4 and 298 K. Initial electrostatic interactions were observed in the minor groove of the duplex, followed directly by aquation to form the monoaqua monochloro species. There was evidence for two discrete monofunctional adducts, through covalent binding at the guanine N7 sites, and one had distinctly different 1H/15N chemical shifts to those observed previously in analogous reactions. Bifunctional adduct formation followed by binding at a second guanine N7 site with evidence for both the 3′–3′ 1,2-GG and 5′–5′ 1,6-GG interstrand cross-links in a ratio of 2 : 1. The results show that cross-link preference is kinetically controlled and will depend critically on the reaction conditions, explaining why in a previous reaction of 1 with duplex I the major adduct isolated by HPLC had two simultaneous 3′–3′ 1,2-interstrand cross-links.
View less >
Journal Title
Dalton Transactions
Volume
42
Issue
9
Copyright Statement
© 2013 Royal Society of Chemistry. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
Subject
Bioinorganic Chemistry
Inorganic Chemistry
Theoretical and Computational Chemistry
Other Chemical Sciences