Nucleic solid phase synthesis

Beausoleil, E., Truong, K.T., Kirshenbaum, K., and Zuckermann, R.N. Influence of monomer structural elements in hydrophilic peptoids. In Innovations and Perspectives in Solid Phase Synthesis and Combinatorial Libraries Peptides, Proteins, and Nucleic Acids, R. Epton (Ed.), 2001, Mayflower Scientific Press Kingswin-ford, UK, pp. 239-242. 

The synthesis and crystal structure of the peptide nucleic acid (PNA) monomer 25 having cyanuric acid as nucleobase have been described. Monomer 25 can be directly used for the solid phase synthesis of PNA oligomers . 

The application of solid-phase synthesis and automation has revolutionized much of the chemical and biochemical research related to peptides and nucleic acids.5 Thus, it is likely that successful methods to synthesize oligosaccharides and glycoconjugates... 

In a recent report, the divergent solid-phase synthesis of nucleic acid dendrimers was also reported and the purity assessed using PAGE [24], however, the details are not included here due to space constraints. 

The ability to synthesize chemically short sequences of single-stranded DNA (oligonucleotides) is an essential part of many aspects of genetic engineering. The method most frequently employed is that of solid-phase synthesis, where the basic philosophy is the same as that in solid-phase peptide synthesis (see Section 13.6.3). In other words, the growing nucleic acid is attached to a suitable solid support, protected nucleotides are supplied in the appropriate sequence, and each addition is followed by repeated coupling and deprotection cycles. 

Other known oligonucleotide analogs include oligomers in which the heterocyclic bases have been modified [155] or replaced by other types of compound [156], Solid-phase syntheses of hybrids of DNA with peptides [157-163], with carbohydrates [164,165], and with PNA (peptide nucleic acids, see Section 16.4.1.2 [166-168]) have also been reported, and several strategies have been developed that enable the preparation of oligonucleotides with a modified 5 - or 3 -terminus [169-174] or of cyclic oligonucleotides [122,175], Various techniques for the parallel solid-phase synthesis of oligonucleotides have been developed for the preparation of compound libraries [176-181],... 

Welz et al. developed a procedure for synthesis of oligoribonucleotides based on application of tetrazole for activation of RNA phosphoramidites in automated solid-phase synthesis <2000MB934>. Ar-Benzoyl tetrazole has been developed as a mild and selective reagent for monobenzoylation of the exocyclic amino group in nucleic acid bases <1997TL8811>. An improved procedure is described for the efficient and high yield (76-91%) synthesis of... 

Epton R. (Ed.), Innovation and Perspectives in Solid Phase Synthesis-Peptides, Proteins and Nucleic Acids, Mayflower Worldwide, Kingswinford, UK, 1994. 

Zhang, L., Goldhammer, C., Henkel, B., et al. (1994) Peptides, proteins and nucleic acids. Biological and biomedical applications, in Innovation and Perspectives in Solid Phase Synthesis (Epton, R., ed.), Mayflower Worldwide Ltd, Birmingham, UK, pp. 711-716. 

Christensen L, Fitzpatrick R, Gildea B, Petersen KH, Hansen HF, Koch T, Egholm M, Buchardt O, Nielsen PE, Coull J, Berg RH. Solid-phase synthesis of pephde nucleic acids. J. Pephde Sci. 1995 3 175-183. 

Building blocks such as compounds 18 and 19 can be used for solid-phase synthesis of peptide-nucleic acids. 

Solid-phase synthesis of nucleic acids. Precise sequences of nucleic acids can be synthesized de novo and used to identify or amplify other nucleic acids. 

Reagent 206 has been prepared that allows disulfide cross-links to be introduced into nucleic acids during solid-phase synthesis. The disulfide is formed between thioalkyl tethers at the N-3-position of thymidines and stabilises the termini of nucleic acid helices. Disulfide linked triplexes have been studied. ... 

Two novel phosphoramidite derivatives of 2 -deoxynucleosides incorporating a pyranose-modified nucleic base have been synthesised and incorporated into short DNA sequences. The galactose-modified deoxyuridine phosphoramidite (52) was synthesised via a Heck reaction between 3, 5 -0,0-bis(tcrt-butyl-dimethylsilyl)-5-iodo-2 -deoxyuridine and 2,3,4,6-tetraacetyl-l-(6-hex-1-ynyl) galacto-pyranoside. Subsequent deprotection, 5 -0-tritylation and treatment with 2-0-cyanoethyl-iV,N-diisopropyl chlorophosphine in the presence of DIPEA offered (52) which was used for solid-phase synthesis of a new type of oligo DNA-galactose conjugate." ... 

Since Nielsen et al introduced peptide nucleic acids (PNA), this area has received vast attention, and continues to do so. More recently, the main area of interest has been in novel analogues, and many new ones have been reported. The solid phase synthesis of DNA-3 -PNA chimeras have been described, in which the DNA is attached to the amino terminal of the PNA via the 3 -phosphate or thiophosphate. All chimeras were shown to have superior thermal stability towards either DNA or RNA than a DNA oligomer, and the phosphodiester linkage was more stable than the phosphorothioate. Hybridisation studies with PNA and PNA-DNA chimeras demonstrate that there is a sequence effect for the junction between PNA and DNA on duplex stability. A decamer pyrimidine bis-PNA oligomer, separated by a linker, when targeted to complementary dsDNA formed three distinct structures. One structure contained two bis-PNA units, and the other two were believed to be structural isomers. 

The inevitable comparison of polysac-chrides to other biopolymer types helps put the challenge into perspective. Nucleic acids are made in a linear manner through chemical and biological synthetic techniques. Likewise, protein sequences are also linear and can be easily determined, produced, and manipulated through a combination of recombinant DNA technology and solid phase synthesis. 

L Zhang, C Goldammer, B Henkel, F Ziihl, G Panhaus, G Jung, E Bayer. In R Epton, ed. Innovation and Perspectives in Solid Phase Synthesis. Peptides, Proteins and Nucleic Acids. Biological and Biomedical Applications. Birmingham, UK Mayflower Worldwide, 1994, pp 711-716. 

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