2.7- Dimethylguanosine

C12H18N505+,I 1,7-Dimethylguanosine iodide (DMGUNI10)343 C15H11ClN3Pt+,C10H13N5O7P--2.25 H20 Chloro(terpyridyl)plati-... 

This chapter briefly describes the general methodology for making both series of ARCAs and describes in detail the synthesis of two representative compounds P1-guanosine-5/ P3-(7,3/-0-dimethylguanosine-5/) triphosphate (Fig. 11.1, compound 2) and P1-guanosine-5/ P3-(7,3/-0-dimethyl-guanosine-5 ) /by- methylene-triphosphate (Fig. 11.1, compound 5). 

Figure 10.29 Diagram of tRNA from yeast, specific for alanine. I, inosine V pseudouridine mG, methylguanosine m2G, dimethylguanosine T, ribothymidine hU, dihydrouridine ml, methylinosine.

Increased levels of pseudouridine have been reported to be present in the urine of patients with various types of cancer (Al, M20, Wl, W2). Since pseudouridine is only found in RNA, Kuo et al. (K38) developed a sensitive RPLC method for the rapid determination of urine pseudouridine levels. In a study of 10 colon cancer patients, they reported that 9 exhibited higher than normal pseudouridine-to-creatinine ratios. Davis et al. (D2) have also investigated urine ribonucleoside distribution patterns in patients with advanced colon cancer and report increased levels of I-methylinosine, 1-methylguanosine, 2-methyIguanosine, adenosine, and N. N -dimethylguanosine when compared to normal urine controls. Figure 17 illustrates the advanced colon cancer and normal urine chromatographic profiles. 

Gehrke s group (G4) analyzed the urine of breast cancer and leukemia patients by RPLC. They report elevated levels of N -acetylcytidine in the breast cancer samples. They also report similar findings of elevated levels of N, N -dimethylguanosine, 1-methylguanosine, 1-methylinosine, and pseudouridine in the urine of patients with Burkitt s lymphoma, lung, colon, breast, and other types of cancer (Wl, W2). 

In the sera of patients with breast cancer, Krstulovic t al. (K28) found 1-methylinosine and N ,N -dimethylguanosine in increased concentrations. They also report on the presence of these compounds in the sera of patients with benign breast tumors, however, at much lower concentrations. Figure 18 illustrates nonneoplastic serum and breast cancer serum chromatographic profiles. 

This conversion has previously been carried out in two steps on 2-(methylsulfanyl)adenine to give the 2-methylsulfonyladcnine by oxidation with chlorine, followed by alkaline hydrolysis." 7V, iV -Dimethylguanosine 9 can be obtained by treatment of 2-(dimethylamino)-9-( -i>ribo-furanosyl)-6-sulfanylpurine with aqueous hydrogen peroxide and ammonia. ... 

Dimethylamino)-9-( -D-ribofuranosyl)purin-6-ol (A, A -Dimethylguanosine, 9) Typical Procedure ... 

The sequences of nearly one hundred archaeal tRNAs have been deduced from either cloned genes or the purified tRNA species (for a review see ref [5]). Compared to their bacterial and eucaryal homologs, archaeal tRNAs systematically lack ribothymidine and 7-methylguanosine. In addition to modified nucleotides (pseudouridine, 2 -0-methylcytidine, 1-methylguanosine and A, iV -dimethylguanosine) that are also found in bacteria and eucarya, archaeal tRNAs contain unique modified bases not encountered in either of the two other domains [6]. Also, the CCA stems of initiator tRNAs from distant archaea Thermoplasma acidophilum, Halococcus morrhuae, Sulfolobus acidocaldarius) contain an identical stretch of five base pairs that has no counterpart in eucaryal and bacterial initiator tRNAs [7],... 

Fig. 4.4.17. Separation of urine nucleosides on a pBondapak C,, column (0.4x30 cm). Sample 2S 1 urine. Eluent 6% methanol in 0.01 M NH4H2PO4 (pH 5.1). Detection UV 254 nm. Peaks 4 -pseudouridine m A. l-methyladeno ine N, unknown s U. 4 thiouridine m l, I-methylinosine m G. 1-methylguanosine ac C, 4-acetylcytidine m G. A( -methylguanosine 2-Me2Gua, N. W -dimethyl-guanine A, adenosine m2G.Af. N -dimethylguanosine. Reprinted from Ref. 79 with permission.

Hypermethylated guanosine-capped mRNA molecules are important in cellular transport and RNA splicing. The chemical synthesis of a 5 -terminal 2,2,7-trimethylguanosine-capped tri ribobonucleotide has been described by condensation of (185) with (186) in the presence of CDI in 40% yield. The synthesis includes a novel three step synthesis of 2N,2N-dimethylguanosine from guano-sine. The product was characterised by proton and phosphorus NMR. 

CigHigNjOs "" " 1,7-Dimethylguanosine iodide (DMGUNIIO) C,5HiiClN3Pf -CioHi3N507l -2.25 H2O Chloro(terpyridyl)plati-num(II)adenosine 5 -monophosphate, hydrate (TPTAMP) ... 

Figure 29-2. Sequence and projection of the conformation of the phenyl alanine specific f-RNAP " of yeast. D, Dihydrouridine DiMeG, 2,2-dimethylguanosine 2 OMeC, 2 methyl cytidine ij/, pseudo-uridine (base bonded to the sugar group via C ).

In conclusion urinary excretion of newborn and amniotic fluid concentrations of 1-methylinosine, 1-methylguanosine, N -methyl-guanosine and N -dimethylguanosine may provide an index of fetal tRNA turnover and thereby of growth. 

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