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Inorg Chim Acta, , ü Brouwer J, van de Putte P, Fichtinger-Schepman AM, Reedijk J. Base-pair substitution hotspots in GAG and GCG nucleotide sequences in Escherichia coli K induced by cis-diamminedichloroplatinum II.

Proc Natl Acad Sci USA, , ü Takahara PM, Rosenzweig AC, Frederick CA, Lippard SJ. Crystal structure of double-stranded DNA containing the major adduct of the anticancer drug cisplatin.

Nature, , ü van Garderen CJ, van Houte LP. Eur J Biochem, , ü Huang H, Zhu L, Reid BR, Drobny GP, Hopkins PB. Solution structure of a cisplatin-induced DNA interstrand cross-link.

Science, , ü Fichtinger-Schepman AM, van der Veer JL, den Hartog JH, Lohman PH, Reedijk J. Adducts of the antitumor drug cis-diamminedichloroplatinum II with DNA: formation, identification, and quantitation.

Biochemistry, , ü Eastman A. Reevaluation of interaction of cis-dichloro ethylenediamine platinum II with DNA.

Biochemistry, , ü ??? A short history of SHELX. Acta Crystallogr A, , ü DeLano WL. The PyMOL Molecular Graphics System DeLano Scientific, San Carlos, CA, USA.

The crystal and molecular structure of cis-diammine-1,1-cyclobutanedicarboxoplatinum II [cis-Pt NH3 2CBDCA]. Dynamic puckering of the cyclobutane ring.

J Mol Struct, , 97ü 22 23 24 International Tables for Crystallography. Dordrecht: Kluwer Academic Publishers, Improved methods for building protein models in electron density maps and the location of errors in these models.

Acta Crystallogr A, , ü Brunger AT. XPLOR Manual, version 3. Structural studies of dicycloplatin?

Much research has been conducted over the past decades in order to prepare drugs such as cisplatin and carboplatin with improved efficacy and reduced toxicity.

Based on the premise that supramolecular platinum agents may have superior physicochemical properties, we successfully designed a novel anticancer agent, dicycloplatin, which has proven to be active against a number of human malignancies.

The crystal structure of dicycloplatin has been determined. An aqueous solution of dicycloplatin was also studied using electrospray ionization mass spectrometry ESI-MS.

Based on the experimental observations, a model of the structure in aqueous solution is proposed which explains both the higher solubility and higher stability of dicycloplatin compared with carboplatin.

June Vol. The compound was approved by the US Food and Drug Administration FDA in and has been used to treat a variety of human malignancies in the past decades [3].

In the course of the therapeutic application, serious consideration must be given to its side effects including nephrotoxicity, neurotoxicity, ototoxicity, nausea and vomiting [4].

In order to overcome these disadvantages, tremendous research efforts have been made in an attempt to find analogues with reduced toxicity and higher efficacy.

More than analogues have been synthesized and screened up to now [5]. However the remaining side effects and the cross-resistance with cisplatin have limited its clinical use [7].

The primary biological target of platinum anticancer agents is DNA [8—12]. Earlier studies have shown that divalent platinum compounds with anticancer activity can be represented using a?

Science China Press and Springer-Verlag Berlin Heidelberg chem. Sci China Chem June Vol. These compounds have several structural features in common [18]: 1 Pt II in an approximate square planar coordination with ligands in cis configuration; 2 The presence of a negatively charged leaving group X with moderate displacement activity in coordination with either a bidentate or two monodentate ligands; 3 The remaining group A is either NH3 or other amine groups; 4 The compound is neutral.

The solubility, lipophilicity and stability of platinum anticancer agents have a direct bearing on their activity and toxicity. Hydrolysis of platinum anticancer compounds is believed to take place when the drug molecules pass from the blood plasma to the cell cytoplasm, where the concentration of chloride is lower than in the blood plasma.

It has been shown that complexes with weak ligands, such as the nitrate ion, hydrolyse rapidly after injection and have been proven to be inactive in vivo.

On the other hand, strong ligands, such as the cyanide ion, bind too tightly to platinum and will not leave sufficiently readily to make the agent active in vivo.

It has been shown that only neutral platinum II complexes with relatively inert ligands possess antitumor activity.

In this paper, we report the crystal structure of a novel anticancer supramolecule, dicycloplatin cis-diammine 1,1cyclobutane dicarboxylate platinum II :1,1 cyclobutane dicarboxylic acid complex , which has been designed to overcome the stability problem of traditional platinum- based agents.

A structural model of dicycloplatin in aqueous solution is proposed based on experimental data. This structural model explains the reasons for the higher solubility and stability of dicycloplatin in water solution.

Preclinical studies have revealed the strong anticancer activity of dicycloplatin. Phase I and Phase II clinical trials have been finished and the results will be published separately.

The refined structure of dicycloplatin has been deposited at the CCDC Cambridge Crystallographic Data Centre ; the reference code is CCDC The crystallographic data, the cell parameters and the refined R-indices of carboplatin and dicycloplatin are given in Table 1.

The structure of carboplatin Figure 1 appears to be identical to the published result [21]. The molecular structure of carboplatin possesses a mirror plane which is located on the plane consisting of the Pt atom and the 1,1-cyclobutyl group.

The average bond angle in the cyclobutane ring is 90q resulting in strong strain within the ring. The coordinated atoms of the ligands and the Pt II center are located in the same plane, which is perpendicular to the cyclobutane ring.

In the crystal, a hydrogen bond is formed between a carboxylate oxygen atom and the NH3 group from a neighboring molecule. With a distance between the proton donor and the acceptor of about 0.

The crystal structure of dicycloplatin shows that it consists of molecules of carboplatin and cyclobutane-1,1-dicarboxylic Table 1 Crystal data and structure refinement for carboplatin and dicycloplatin 2 Materials and methods Carboplatin Dicycloplatin C12H20N2O8Pt Crystals of carboplatin were obtained from a saturated aqueous solution at room temperature.

A total of reflections were collected. The structures were solved and refined using Shelx [19]. Graphical representations of the structures were produced using the program PyMol unless otherwise specified [20].

Figure 3 The structure of the cyclobutane-1,1-dicarboxylic acid moiety in dicycloplatin. Both carboplatin and the CBDC are neutral and the molecular ratio is The carboplatin moiety in the dicycloplatin structure is virtually identical to that in carboplatin Figure 2.

The structure of the cyclobutane-1,1-dicarboxylic acid moiety is shown in Figure 3. This is due to the formation of strong intermolecular hydrogen bonds.

Dicycloplatin is composed of carboplatin and CBDC, which are linked through strong hydrogen bonds and can therefore be regarded as a supramolecule.

Two types of hydrogen bonds were observed in the crystal structure. O hydrogen bonds with the carboxyl oxygen atoms of carboplatin, with the distances between the donor oxygen and acceptor oxygen atoms being 0.

O hydrogen bonds with the carboplatin molecule located between them. This hydrogen bonding scheme is repeated along the b axis leading to the formation of a one-dimensional chain polymer of carboplatin and CBDC.

Another type of hydrogen bond is formed between the NH3 groups of carboplatin and the oxygen atoms of CBDC.

The distance between the nitrogen and oxygen atoms is around 0. O hydrogen bonds giving rise to a two-dimensional planar polymer of the dicycloplatin supramolecule.

The plane of the two-dimensional dicycloplatin supramolecule is parallel to the crystallographic ab plane. In the electrospray mass spectrum ESI-MS of dicycloplatin in aqueous solution Figure 6 , an M-1 peak Figure 2 The structure of the carbop1atin moiety in dicycloplatin.

Figure 4 The one-dimensional hydrogen bonded polymer structure of dicycloplatin along the b axis. YANG XuQing, et al. Skip to main content. Currently unavailable.

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Г¶wd scrapedfeeds.com - магазин товаров для творчества. Самые низкие цены на весь товар, доставка в любую страну. Maxim Trydub Для всех 4 д. Запись из ленты пользователя Maxim Trydub Отпугиватель кротов на солнечны. Sɛ" g_9Vjs 2 ' M`` = i b Y n ; (&J g + m i?[Ox G PVC +a پW 7QC JTĆ >)6 } %h |5;^ $ W a =!` ~ ؟A + _ '^u gp g Fw y 3 ܜ -$ = 2 Г WD G ƻ +j vx " r h0 @ P ¦ 7 ^ * 93 /+h X12 r* z! c _ p > ኱ B Vyj gb Y s C J9 e ; FX% e-"b *R M 7 oV ܱ'n)Zf ^ i ؏q Xqέ*.܇ ĭrz z & j i% u q܎␳ p(O Xj 4햻 V i { c? ͥ{ 8|V >* c * px o [email protected] e # f 5m. ssd диски. Тип: для ноутбука по низкой цене от грн в интернет магазине scrapedfeeds.com Более моделей Гарантия качества Оплата частями Доставка по всей Украине ☎ +38 () Звоните!. ssd диски. Тип: для ноутбука по низкой цене от грн в интернет магазине scrapedfeeds.com Более моделей Гарантия качества Оплата частями Доставка по всей Украине ☎ +38 () Звоните!. Ahutek llmankäsittelykoneet ja teollisuuspuhaltimet AakkulantieFI KANGASALA. HTK-Went Polska Sp. Zitat von DieterVfB Zitat von st3in Zitat von und woher nimmt der AR die kompetenz das zu beurteilen? Figure 4 The one-dimensional hydrogen bonded polymer structure of dicycloplatin along Г¶wd b axis. The energy of the model was then minimized using the program XPLOR [24]. It has been shown that complexes with weak ligands, such as the nitrate ion, hydrolyse rapidly after injection and have been proven to be inactive in vivo. J Med,Fash N Chips Yarbro CH. Ann Intern Med,— Barabas K, Milner R, Lurie D, Adin C. With a distance between the proton donor and the acceptor of about 0. The structure of the cyclobutane-1,1-dicarboxylic acid moiety is shown in Figure 3. Acta Crystallogr A,— Brunger AT. Eur J Biochem,ü Huang H, Zhu L, Reid BR, Drobny GP, Hopkins PB. We don't know when or if this item will be back Г¶wd stock. On the other hand, 1001 Spiele Kostenlos Bubbles ligands, such as the cyanide ion, bind too tightly to platinum and will not leave sufficiently readily to make the agent active in vivo. Proc Natl Acad Sci USA,— Takahara PM, Rosenzweig AC, Frederick CA, Lippard SJ. Amazon Renewed Like-new products you can trust.

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