Binding of cis- and trans-dichlorodiammineplatinum(II) to nucleosides.i.  Location of the binding sites

Mansy, Samir; Rosenberg, Barnett; Thomson, Andrew J.

doi:10.1021/ja00786a045

Cited by 172 publications

(46 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6e) The second step is not observed in any other combination of the porphyrins with the nucleotides except for 4a with poly(dG)-poly(dC). Since a gradual change similar to the second step has been reported in the case of CDDP with GMP, 12) we propose that the second step is due to coordination of GMP to Pt in 4a.…”

Section: Reactions Of Porphyrins With Nucleotidessupporting

confidence: 73%

See 1 more Smart Citation

Synthesis and Nucleic Acid-Binding Properties of Water-Soluble Porphyrins Appending Platinum(II) Complexes.

Munakata

Kanzaki

Nakagawa

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

There has been considerable interest in understanding the binding of the antitumor drug cis-dichlorodiammine platinum(II) (CDDP) and its analogs to their putative target DNA in cancer cells.1) Platinum complexes can bind rapidly to nucleic acids (including DNA) in aqueous solution and therefore are useful as a functional group to design artificial receptors for DNA. The anti-cancer activity of CDDP arises from its ability to damage DNA by forming a major adduct with intrastrand d(GpG) and d(ApG) crosslinks.2) These crosslinks of CDDP to d(GpG) and d(ApG) bend and unwind the duplex, and then the altered structure attracts high-mobility-group (HMG) domain proteins.3) This binding of HMGdomain proteins to CDDP-modified DNA has been postulated to mediate the antitumor properties of the drugs. 4)Studies on the binding of cationic porphyrins to DNA have been of great significance to those working in cancer research and gene technology. 5) Some cationic porphyrins bearing quaternary ammonium salt units such as ammonium or pyridinium groups can act as binders for DNA. Several researchers have investigated how cationic porphyrins bind to DNA in groove or outside binding on the basis of Coulomb and/or hydrophobic interactions.5a,c,6) We designed and synthesized two water-soluble porphyrins appending platinum(II) complexes and studied their reactions with a variety of DNA and nucleic acids. In the porphyrins, cationic groups of the appended platinum(II) complex solubilize the porphyrins to water and provide coordination ability for binding to DNA. Furthermore, because the cationic porphyrins can also bind to DNA, the platinum(II) complexes appended by the porphyrins are expected to function additively with the porphyrins and then bind strongly to DNA.This report describes the synthesis of two derivatives of 5,15-bis(o-substituted phenyl)porphyrin appending two chlorodiammineplatinum(II) complexes at the ortho position of the two phenyl rings of the porphyrin (see 4a and 4b in Fig. 1). We then studied their reactions with a variety of nucleic acids [disodium adenosine-5Ј-monophosphate (AMP), disodium guanosine-5Ј-monophosphate (GMP), disodium thymine-5Ј-monophosphate (TMP), disodium cytidine-5Ј-monophosphate (CMP), synthetic polymer poly(dG)-poly(dC), poly(dA)-poly(dT)] using 1 H-NMR, UV-vis or FAB-MS spectroscopies. Results and DiscussionSyntheses and Characterization of Water-Soluble Porphyrins Appending Platinum(II) Complexes or Quaternary Ammonium Groups Syntheses of the water-soluble porphyrins with two platinum(II) complexes are outlined in Fig. 1. Condensation of (tetramethyldipyrryl)methane 7) with o-phthalaldehydic acid gave porphyrinogen 1 in a good yield. Oxidation of the porphyrinogen to porphyrin 2 was accomplished by using o-chloranil. Because of the limited solubility of 2, the chromatographic separation of the two atropisomers could not be accomplished; it was achieved after deriving to aminoethylcarbamides 3a and 3b. Compound 3b was hydorolyzed with hydrochloric acid (6 M), and a treatment of the hydrolyzed...

show abstract

Section: Reactions Of Porphyrins With Nucleotidessupporting

confidence: 73%

“…This result also supports the successive binding of two guanosine molecules to 4a. The binding site of guanosine to 4a is tentatively assignable to N-7, in analogy with the reaction of trans-[Pt(NH 3 ) 2 Cl 2 ] with guanosine, 12) and a proposed structure is shown in Fig. 11.…”

Section: Uv-vis Spectral Data For Porphyrins In Various Solventsmentioning

confidence: 88%

Synthesis and Nucleic Acid-Binding Properties of Water-Soluble Porphyrins Appending Platinum(II) Complexes.

Munakata

Kanzaki

Nakagawa

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…Reaction suspensions were mixed on an Eppendorf Mixer 5432 at 37°C for 15 h to complete formation of the DNA-small molecule affinity reagents. Literature procedures for the formation of DNA-small molecule complexes were followed to prepare MMC (19), cisplatin (20), and transplatin (20) affinity reagents with the modification that these reactions were mixed on an Eppendorf Mixer 5432 at 37°C for 15 h.…”

mentioning

confidence: 99%

Identification of GAPDH as a protein target of the saframycin antiproliferative agents

Xing

LaPorte

Barbay

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Saframycin A (SafA) is a member of a class of natural products with potent antiproliferative effects in leukemia-and tumor-derived cells. This activity is frequently conjectured to derive from the ability of saframycins to covalently modify duplex DNA. We used a DNA-linked affinity purification technique to identify GAPDH as a protein target of DNA-small molecule adducts of several members of the saframycin class. Nuclear translocation of GAPDH occurs upon treatment of cancer cells with saframycins, and depletion of cellular GAPDH levels by small interfering RNA transfection confers drug resistance. Roeder and coworkers have recently suggested that GAPDH is a key transcriptional coactivator necessary for entry into S phase. Our data suggest that GAPDH is also capable of forming a ternary complex with saframycin-related compounds and DNA that induces a toxic response in cells. These studies implicate a previously unknown molecular mechanism of antiproliferative activity and, given that one member of the saframycin class has shown efficacy in cancer treatment, suggest that GAPDH may be a potential target for chemotherapeutic intervention.

show abstract

“…In studies involving cis-dichlorodiammine platinum(ll), (cis-DDP), Pt(I1) binds preferentially at the N(7) position of guanine residues (25). However, in other experiments, when attempts are made to strip platinum off the DNA strand with cyanide ion, the small fraction of the metal which remains is bound to thymine residues (26).…”

Section: Resultsmentioning

confidence: 99%

The reaction of chloro(triphenylphosphine)gold(I) with 1-methylthymine

Faggiani¹,

Howard-Lock²,

Lock³

et al. 1987

Can. J. Chem.

View full text Add to dashboard Cite

Can. J. Chem. 65, 1568 (1987). 1-Methylthyminato-N 3-triphenylphosphinegold(~) was prepared by reacting chloro(triphenylphosphine)gold(I) with 1-methylthymine in aqueous methanol at pH 11. The product was examined by X-ray crystallogra~hy and was foundJo have the orthorhombic space group C222' (no. 20) with cell dimensions a = 12.760(7) A, b = 1 1.530(2) A, c = 31.893(5) A, and eight formula units in the unit cell. Data were collected with use of M o K a radiation and a Syntex P2, diffractometer. The crystal structure was determined by standard methods and refined to R = 0.1 12 and R,,. = 0.076 on the basis of 4760 unique reflections. Bond lengths and bond angles are normal. Packing in the crystal lattice is dominated by the triphenylphosphine rings which arrange roughly as blades of a propellor and are the source of the crystal's chirality. The title and related compounds were also examined by 'H nmr, I3c nmr, and vibrational spectroscopy.

show abstract

Binding of cis- and trans-dichlorodiammineplatinum(II) to nucleosides.i. Location of the binding sites

Cited by 172 publications

References 5 publications

Synthesis and Nucleic Acid-Binding Properties of Water-Soluble Porphyrins Appending Platinum(II) Complexes.

Synthesis and Nucleic Acid-Binding Properties of Water-Soluble Porphyrins Appending Platinum(II) Complexes.

Identification of GAPDH as a protein target of the saframycin antiproliferative agents

The reaction of chloro(triphenylphosphine)gold(I) with 1-methylthymine

Contact Info

Product

Resources

About