Monofunctional trans-PtII(NH3)2 modification of pyrimidine-rich deoxyoligonucleotides: direct platination and use of a protective group

Berghoff, Ulrich; Schmidt, Kathrin; Janik, Matthias; Schröder, Guy; Lippert, Bernhard

doi:10.1016/s0020-1693(97)05779-4

Cited by 13 publications

(5 citation statements)

References 22 publications

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“…Relevance of Model Compounds to Metalated DNA Triplexes. As part of ongoing work in our laboratory to apply metal cross-linking of nucleic acid strands to antigene and antisense strategies 5a,51,52 and to obtain models of relevant adducts, , we have previously concentrated primarily on metalated triplexes of the type pym × pu·pym (first pym of third strand added to Watson−Crick pu·pym duplex). 5a, …”

Section: Resultsmentioning

confidence: 99%

“…As part of ongoing work in our laboratory to apply metal cross-linking of nucleic acid strands to antigene and antisense strategies 5a, 51,52 and to obtain models of relevant adducts, 1,12 we have previously concentrated primarily on metalated triplexes of the type pym × pu‚pym (first pym of third strand added to Watson-Crick pu‚pym duplex). 5a, 51 The two established G′ × G‚C triplets (Figure 8a,b) contain the G′ × G pairs III and II, respectively, of Figure 7. The orientation of the third strand containing G′ is dictated by the sugar conformation of this base (anti or syn).…”

Section: Relevance Of Model Compounds To Metalated Dnamentioning

confidence: 99%

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Metal-Modified Base Pairs Involving Different Donor Sites of Purine Nucleobases: trans-[a₂Pt(7,9-DimeG-N1)(9-EtGH-N7)]²⁺andtrans-[a₂Pt(7,9-DimeG-N1)(9-EtG-N7)]⁺(a = NH₃or CH₃NH₂; 9-EtGH = 9-Ethylguanine; 7,9-DimeG = 7,9-Dimethylguanine). Possible Relevance to Metalated DNA Triplex Structures

et al. 1999

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The X-ray crystal structures of four mixed-nucleobase complexes 1a, 1b, 2, and 4 of trans-a2PtII (a = NH3 or CH3NH2) with N1-bonded 7,9-dimethylguanine (7,9-DimeG) and N7-bonded 9-ethylguanine (9-EtGH) are reported. The compounds are discussed in terms of their possible model character for platinated nucleobase triplets of the pu × pu·pym (pu = purine, pym = pyrimidine) type and are compared with known guanine·guanine pairs. Structural differences resulting from a “metal modification” have been studied, as have been stacking and H bonding motifs. 1a and 1b are two modifications of the same compound, trans-[(NH3)2Pt(7,9-DimeG)(9-EtGH)](ClO4)2·H2O. X-ray data for 1a: orthorhombic, Pca21, a = 13.833(3) Å, b = 14.357(3) Å, c = 13.293(3) Å, Z = 4, R = 0.027. 1b: monoclinic, P21/n, a = 13.987(3) Å, b = 12.582(3) Å, c = 15.613(3) Å, β = 104.61(3)°, Z = 4, R = 0.034. trans-[(CH3NH2)2Pt(7,9-DimeG)(9-EtGH)](ClO4)2 (2): orthorhombic, Pca21, a = 13.886(1) Å, b = 14.698(1) Å, c = 13.008(3) Å, Z = 4, R = 0.034. trans-[a2Pt(7,9-DimeG)(9-EtG)](ClO4)·nH2O (3, a = NH3, n = 2; 4, a = CH3NH2, n = 3). X-ray data for 4: monoclinic, C2/c, a = 23.296(5) Å, b = 10.566(2) Å, c = 22.327(4) Å, β = 93.73(3)°, Z = 8, R = 0.047. The metalated base triplet 2·(1-MeC) (1-MeC = 1-methylcytosine) has been detected in DMSO-d 6 solution through 1H NMR spectroscopy, and an ab initio optimized structure of an analogous platinated base triplet has been obtained.

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Section: Resultsmentioning

confidence: 99%

Section: Relevance Of Model Compounds To Metalated Dnamentioning

confidence: 99%

Metal-Modified Base Pairs Involving Different Donor Sites of Purine Nucleobases: trans-[a₂Pt(7,9-DimeG-N1)(9-EtGH-N7)]²⁺andtrans-[a₂Pt(7,9-DimeG-N1)(9-EtG-N7)]⁺(a = NH₃or CH₃NH₂; 9-EtGH = 9-Ethylguanine; 7,9-DimeG = 7,9-Dimethylguanine). Possible Relevance to Metalated DNA Triplex Structures

et al. 1999

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“…Single-strand DNA exists in telomeres and also in the normal course of DNA biochemistry. Also, understanding ss adducts may eventually prove to be of direct importance in assessing the structure and mechanism of Pt-containing antisense oligo drugs. ,, However, the more immediate relevance of the current work is the assessment of the possible role of the right-handed HH1 cross-link in influencing the distortions in DNA duplexes, especially the factors contributing to the unusually large positive slide and shift of the 5′-XG* bp step. The most abundant long-lived conformer observed for all ( R , S , S , R )-BipPt(oligo) adducts studied here is the right-handed HH1 conformer.…”

Section: Discussionmentioning

confidence: 99%

Origins of the Distortions in the Base Pair Step Adjacent to Platinum Anticancer Drug−DNA Adducts. Fundamental NMR Solution Studies Utilizing Right-Handed Cross-Link Models Having 5′- and 3′-Flanking Residues

2009

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For DNA duplexes, the Lippard laboratory has shown that the XG* base pair (bp) step has a very unusual slide and shift, where G* is a G platinated at N7 by di- or monofunctional platinum anticancer drugs. One approach toward understanding the cause of this important unexpected XG* distortion is to examine single-strand (ss) oligonucleotide (oligo) models. Both duplex and ss XG*G* models of the key G*G* cross-link formed by cisplatin have the HH1 conformation with head-to-head bases. Cross-links have R canting (3'-G* H8 atom toward 5'-G*) in duplexes and L canting (5'-G* H8 atom toward 3'-G*) in ss models. However, dynamic motion in solution makes the ss features difficult to define. Thus, we employ less dynamic cross-link models such as (R,S,S,R)-BipPt(d(TG*G*)) and (R,S,S,R)-BipPt(d(pG*G*TTT)), the first examples of an HH1 conformer with R canting for ss oligos longer than d(GpG) (Bip = 2,2'-bipiperidine). In these, the 5'-T residue decreases R canting (indicating steric clashes with the 5'-G*) and the less bulky 5'-phosphate group forms a H-bond to HN-Pt (indicating that R canting allows H-bonding). We conclude that the 5'-X residue in duplex adducts changes its position from that in B form DNA to avoid steric clashes with the 5'-G* and the carrier ligand and secondarily to form a Watson-Crick base pair. These features, possibly aided by weak carrier-ligand H-bonding, lead to the relatively unusual features distinctive to the "Lippard bp step".

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“…A major limiting factor for the successful application of this principle for in vivo gene regulation is the lack of an efficient synthesis of site‐specifically trans ‐Pt II ‐modified deoxyoligonucleotide (analogues). Studies directed to this aim14, 22 have been pursued and significant progress has already been achieved by incorporation of preplatinated building blocks into oligonucleotides by solid‐phase DNA‐synthesis methodologies 23–25. However, a really efficient method is not yet available.…”

Section: Introductionmentioning

confidence: 99%

Monofunctionally trans ‐Diammine Platinum( II )‐Modified Peptide Nucleic Acid Oligomers: A New Generation of Potential Antisense Drugs

Schmidt

Boudvillain

Schwartz

et al. 2002

Chemistry A European J

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Rotaxane molecular shuttles were studied in which a tetralactam macrocyclic ring moves between a succinamide station and a second station in which the structure is varied. Station 2 in all cases is an aromatic imide, which is a poor hydrogen‐bond acceptor in the neutral form, but a strong one when reduced with one or two electrons. When the charge density on the hydrogen‐bond‐accepting carbonyl groups in station 2 is reduced by changing a naphthalimide into a naphthalene diimide radical anion, the shuttling rate changes only slightly. When station 2 is a pyromellitimide radical anion, however, the shuttling rate is significantly reduced. This implies that the shuttling rate is not only determined by the initial unbinding of the ring from the first station, as previously supposed. An alternative reaction mechanism is proposed in which the ring binds to both stations in the transition state.

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Monofunctional trans-PtII(NH3)2 modification of pyrimidine-rich deoxyoligonucleotides: direct platination and use of a protective group

Cited by 13 publications

References 22 publications

Origins of the Distortions in the Base Pair Step Adjacent to Platinum Anticancer Drug−DNA Adducts. Fundamental NMR Solution Studies Utilizing Right-Handed Cross-Link Models Having 5′- and 3′-Flanking Residues

Monofunctionally trans ‐Diammine Platinum( II )‐Modified Peptide Nucleic Acid Oligomers: A New Generation of Potential Antisense Drugs

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Monofunctional trans-PtII(NH3)2 modification of pyrimidine-rich deoxyoligonucleotides: direct platination and use of a protective group

Cited by 13 publications

References 22 publications

Metal-Modified Base Pairs Involving Different Donor Sites of Purine Nucleobases: trans-[a2Pt(7,9-DimeG-N1)(9-EtGH-N7)]2+andtrans-[a2Pt(7,9-DimeG-N1)(9-EtG-N7)]+(a = NH3or CH3NH2; 9-EtGH = 9-Ethylguanine; 7,9-DimeG = 7,9-Dimethylguanine). Possible Relevance to Metalated DNA Triplex Structures

Metal-Modified Base Pairs Involving Different Donor Sites of Purine Nucleobases: trans-[a2Pt(7,9-DimeG-N1)(9-EtGH-N7)]2+andtrans-[a2Pt(7,9-DimeG-N1)(9-EtG-N7)]+(a = NH3or CH3NH2; 9-EtGH = 9-Ethylguanine; 7,9-DimeG = 7,9-Dimethylguanine). Possible Relevance to Metalated DNA Triplex Structures

Origins of the Distortions in the Base Pair Step Adjacent to Platinum Anticancer Drug−DNA Adducts. Fundamental NMR Solution Studies Utilizing Right-Handed Cross-Link Models Having 5′- and 3′-Flanking Residues

Monofunctionally trans ‐Diammine Platinum( II )‐Modified Peptide Nucleic Acid Oligomers: A New Generation of Potential Antisense Drugs

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