Trinucleotides

Di- and trinucleotides may be used as units instead of the monomers. This convergent synthetic strategy simplifies the purification of products, since they are differentiated by a much higher jump in molecular mass and functionality from the educls than in monomer additions, and it raises the yield. We can illustrate the latter effect with an imaginary sequence of seven synthetic steps, c.g. nucleotide condensations, where the yield is 80% in each step. In a converging seven-step synthesis an octanucleotide would be obtained in 0.8 x 100 = 51% yield, compared with a 0.8 x 100 = 21% yield in a linear synthesis. 

How would the structures of the trinucleotides AUG and GUA of the pentoses are o ribose differ from the trinucleotide in Fig... 

FIGURE 28.1 (a) Structural formula and (b) molecular model of the trinucleotide ATG. 

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

CpCpApCpCpA and this hexanucleotide has been prepared from appropriately protected trinucleotides using a sulphonyl chloride as condensing agent.2 (3 )-0-Glycyl esters of Cpl and dCpA have been prepared as potential substrates of ribosomal peptidyl transferase. While the glycyl ester of Cpl released the polypeptide chain from polylysyl-tRNA in a ribosomal system from E. coli, the dCpA derivative showed little activity. 

Trinucleotides are formed by 5 -deprotection of the dinucleotide and subsequent conversion with the monotriazolide in the presence of N-methylimidazole. The fully protected di- and trideoxyribonucleotides of the following nucleotide sequences have been obtained in high yield T-T (82%), C-T (88%), C-C (84%), CM3 (81%), G-T (83%), A-G-T (65%), C-G-T (61%). The yields are similar to those obtained in a reaction involving l-(triisopropylbenzenesulfonyl)tetrazole as coupling agent(see also Section 12.7). 

In ref. [123], 1-triisopropylbenzenesulfonyl- or mesitylenesulfonyl-5-(pyridine-2-yl)-tetrazole (VIII) was successfully used as a coupling agent for the synthesis of protected di- and trinucleotides. In comparison with the sulfonic acid tetrazolides these are able to achieve a stereoselective synthesis of dinucleoside monophosphate aryl esters. 311 1241... 

Comparing reaction times and yields for the condensing agents 1-triisopro-pylbenzenesulfonyl-4-nitroimidazole, mesitylenesulfonyl-3-nitro-1,2,4-triazole, 1 -triiso-propylbenzenesulfonyl-3-nitro-1,2,4-triazole, and 8-quinolinesulfonyl-3-nitro-1,2,4-triazole, the latter showed the highest yield and shortest reaction time. A fully protected 2, 5 -trinucleotide diphosphate was also successfully synthesized by means of a mixture of 8-quinolinesulfonyl chloride and 3 -nitro-1,2,4-triazole,[ 1421... 

Wang Q, Raytchev M, Fiebig T (2007) Ultrafast energy delocalization and electron transfer dynamics in 2-aminopurine-containing trinucleotides. Photochem Photobiol 83 637-641... 

A d(5 -CCGp)—the 5 end of the trinucleotide is protected as the methyl ester, while the 3 end carries a phosphate group activated by the condensation... 

The attachment of the two trinucleotides A and B to the matrix takes place via Watson-Crick base pairing they approach each other in such a manner that the formation of the S -S -phosphodicster bond can occur. The nature of the trinucleotide sequence chosen means that the new hexanucleotide formed at the matrix has the same sequence as the matrix itself. After its separation from the original matrix, the newly formed hexamer can itself function as a matrix. 

La Spada, A. R., Roling, D. B., Harding, A. E. et al. Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nat. Genet. 2 301-304,1992. 

Dentatorubalpallidoluysian atrophy (DRPLA) Autosomal dominant CAG trinucleotide repeat... 

Huntington s Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington s disease chromosomes. Cell 72 971-983,1993. 

Ikeuchi, T., Koide, R., Tanaka, H. et al. Dentatorubral pallidoluysian atrophy clinical features are closely related to unstable expansions of trinucleotide (CAG) repeat. Ann. Neurol. 37 769-775,1995. 

Scheuermann, T., Schulz, B., Blume, A., Wahle, E., Rudolph, R., and Schwarz, E. (2003). Trinucleotide expansions leading to an extended poly-L-alanine segment in the poly (A) binding protein PABPN1 cause fibril formation. Protein Sci. 12, 2685-2692. 

Trinucleotide Repeat Expansion DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats, [nih]... 

Trinucleotide Repeats Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes, [nih]... 

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