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Platination of full length tRNA(Ala) and truncated versions of the acceptor stem and anticodon loop.

Papsai, Pal LU ; Sykfont Snygg, Åse LU ; Aldag, Jasmin LU and Elmroth, Sofi LU (2008) In Dalton Transactions p.5225-5234
Abstract
Nuclear DNA is a well characterized target for many low molecular metal-based drugs, with cisplatin and related antineoplastic compounds as typical examples. Much less is known concerning to what extent targeting of RNA may influence the activity spectrum of these types of drugs. In a preliminary communication by us (Papsai et al., Dalton Trans., 2006, 3515) we were able to show that the folded, three-dimensionally well defined structure of tRNA(Ala) readily interacts with cisplatin. In the present study we have further analyzed the binding preferences within the preferentially targeted stem region (sMh(Ala)) by modulation of the sequence around the G-U wobble base-pair and the net charge of the 3' and 5' ends. Our data show that the... (More)
Nuclear DNA is a well characterized target for many low molecular metal-based drugs, with cisplatin and related antineoplastic compounds as typical examples. Much less is known concerning to what extent targeting of RNA may influence the activity spectrum of these types of drugs. In a preliminary communication by us (Papsai et al., Dalton Trans., 2006, 3515) we were able to show that the folded, three-dimensionally well defined structure of tRNA(Ala) readily interacts with cisplatin. In the present study we have further analyzed the binding preferences within the preferentially targeted stem region (sMh(Ala)) by modulation of the sequence around the G-U wobble base-pair and the net charge of the 3' and 5' ends. Our data show that the adduct profile is strongly influenced by the presence of the 5' end phosphate group. Further, the adduct formation reaction can be prevented by replacement of the G-U wobble base-pair with the fully complementary G-C pair. To further investigate the influence from local sequence on the platination process, a model of the anticodon region (acMh(Ala)) was also investigated. In the absence of consecutive guanine-residues in the stem- and anticodon regions, preferential platination was found to take place at the terminal AG-site in the stem region. However, after introduction of a GG-pair in the anticodon loop, platination was observed also here. At 37 degrees C, pH 6.3 and C(Pt) = 0.10 mM the rate of platination was determined to be ca. 1 x 10(-4) s(-1), with the most rapid reaction observed for interaction with the anticodon model carrying two adjacent guanines in the single-stranded loop. Together, these data show that platination of RNA is highly sequence- and structure-dependent. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Dalton Transactions
issue
38
pages
5225 - 5234
publisher
Royal Society of Chemistry
external identifiers
  • wos:000259411500016
  • pmid:18813377
  • scopus:52349105556
ISSN
1477-9234
DOI
10.1039/b719542g
language
English
LU publication?
yes
id
e667d5e6-0730-4123-96d3-369d3a60d6cc (old id 1242670)
date added to LUP
2009-03-02 09:41:29
date last changed
2017-08-20 03:41:52
@article{e667d5e6-0730-4123-96d3-369d3a60d6cc,
  abstract     = {Nuclear DNA is a well characterized target for many low molecular metal-based drugs, with cisplatin and related antineoplastic compounds as typical examples. Much less is known concerning to what extent targeting of RNA may influence the activity spectrum of these types of drugs. In a preliminary communication by us (Papsai et al., Dalton Trans., 2006, 3515) we were able to show that the folded, three-dimensionally well defined structure of tRNA(Ala) readily interacts with cisplatin. In the present study we have further analyzed the binding preferences within the preferentially targeted stem region (sMh(Ala)) by modulation of the sequence around the G-U wobble base-pair and the net charge of the 3' and 5' ends. Our data show that the adduct profile is strongly influenced by the presence of the 5' end phosphate group. Further, the adduct formation reaction can be prevented by replacement of the G-U wobble base-pair with the fully complementary G-C pair. To further investigate the influence from local sequence on the platination process, a model of the anticodon region (acMh(Ala)) was also investigated. In the absence of consecutive guanine-residues in the stem- and anticodon regions, preferential platination was found to take place at the terminal AG-site in the stem region. However, after introduction of a GG-pair in the anticodon loop, platination was observed also here. At 37 degrees C, pH 6.3 and C(Pt) = 0.10 mM the rate of platination was determined to be ca. 1 x 10(-4) s(-1), with the most rapid reaction observed for interaction with the anticodon model carrying two adjacent guanines in the single-stranded loop. Together, these data show that platination of RNA is highly sequence- and structure-dependent.},
  author       = {Papsai, Pal and Sykfont Snygg, Åse and Aldag, Jasmin and Elmroth, Sofi},
  issn         = {1477-9234},
  language     = {eng},
  number       = {38},
  pages        = {5225--5234},
  publisher    = {Royal Society of Chemistry},
  series       = {Dalton Transactions},
  title        = {Platination of full length tRNA(Ala) and truncated versions of the acceptor stem and anticodon loop.},
  url          = {http://dx.doi.org/10.1039/b719542g},
  year         = {2008},
}