Peptide nucleic acid synthesis

M. Hollenstein, C.J. Leumann, Fluorinated olefinic peptide nucleic acid Synthesis and pairing properties with complementary DNA, J. Org. Chem. 70 (2005) 3205-3217. 

Scheme 9 Possible Side Reactions in Peptide Nucleic Acid Synthesis B...

Scheme 10 Peptide Nucleic Acid Synthesis by the tert-Butoxycarbonyl/Benzyloxycarbonyl Method132-33 ...

Table 1 Peptide Nucleic Acid Synthesis Protocol 32-53 ...

Noncovalent Protection in Solid-Phase Rhodamine-Labeled Peptide Nucleic Acid Synthesis... 

Basu S., Wickstrom E. Synthesis and characterization of a peptide nucleic acid conjugated to a D-peptide analog of insu-lin-like growth factor 1 for increased cellular uptake. Bioconjug. Chem. 1997 8 481-488. 

Fig. 6.12 The synthesis of A-(2-aminoethyl)-glycine, which is required for the construction of peptide nucleic acids. The reaction corresponds to the Stacker synthesis...

The minimal cell, as the simplest system which has all the required properties of life (metabolism, self-reproduction and the ability to evolve), is presently studied as part of a new research discipline synthetic biology. This includes subjects such as synthesis in branches of biological systems, for example, of new RNA species, new peptides and new nucleic acid analogues, as well as the synthesis of peptide nucleic acids. One example is the work of M. R. Ghadiri and G. von Kiedrowski on self-replication of oligonucleotides and oligopeptides (Luisi, 2006b). 

In addition, Dose and Seitz (2005) employed native chemical ligation to synthesize peptide nucleic acids (PNAs) by linking shorter segments of PNAs to make long contiguous strands, which could not be made through typical oligo synthesis procedures. 

Dose, C., and Seitz, O. (2005) Convergent synthesis of peptide nucleic acids by native chemical ligation. Org. Lett. 7(20), 4365-4368. 

Thompson, A., Prescott, M., Chelebi, N., Smith, J., Brown, T., and Schmidt, G. (2007) Electrospray ionisation-cleavable tandem nucleic acid mass tag-peptide nucleic acid conjugates Synthesis and applications to quantitative genomic analysis using electrospray ionisation-MS/MS. Nucleic Acids Res. 35(4), e28. 

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 . 

Virtually all biological reactions are stereospecific. This generalization applies not only to the enzyme-catalyzed reactions of intermediary metabolism, but also to the processes of nucleic acid synthesis and to the process of translation, in which the amino acids are linked in specific sequence to form the peptide chains of the enzymes. This review will be restricted mainly to some of the more elementary aspects of the stereospecificity of enzyme reactions, particularly to those features of chirality which have been worked out with the help of isotopes. 

The synthesis of DNA analogues with a backbone of poly(/V-(2-amino-ethyl)glycine) (peptide nucleic acids = PNA) instead of phosphate-ribose, which were introduced into affinity labeling by Egholm et al. (28), opened up several new applications for affinity separations (23,28-42). Since this backbone is by far less polar, the behavior of the monomer as well as that of DNA/PNA hybrids is largely different, allowing the complete separation of affinity complexes. In addition, it seems that the stability of duplexes is... 

A synthesis of the monomeric unit 128 of a peptide nucleic acid analog (PNA) offers an example of stereospecific cross-coupling of a Reformatsky reagent with (Z)-vinylic iodide 126. The coupling reaction of the preformed Reformatsky reagent prepared in dimethoxymethane (methylal) with 126 is carried out using 8% of Pd(PPh3)4 in DMPU as the solvent at 65 °C to afford 127 (equation 70)161. 

An array of oligonucleotide which is composed of 20 80-mer oligos, or peptide nucleic acid probes, is synthesized either in situ (i.e., on-chip) or using conventional synthesis followed by on-chip immobilization. The resultant DNA array is then exposed to the labeled sample of DNA, hybridized, and the identity/abundance of complementary sequences determined. This method was developed at Affymetrix, Inc. and called DNA chips. Today, oligonucleotide-based chips are manufactured by many companies using alternative in situ synthesis or depositioning technologies. 

Synthesis of the Pseudoisocytosine Peptide Nucleic Acid Monomer... 

Scheme 6 Synthesis of the 2,6-Diamino-9//-purine Peptide Nucleic Acid Monomer1261...

Scheme 7 Synthesis of the D-Lysine Peptide Nucleic Acid Monomed281...

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],... 

While no examples of automated solid-phase oligosaccharide synthesis had been reported until the work described here,2 automated oligosaccharide synthesis was predated by efficient methods for the synthesis of peptides3 and nucleic acids.4 Here we briefly discuss the general features of each method, with particular emphasis on the scale and efficiency of peptide and nucleic acid synthesis. 

The demonstration that the polymerase chain reaction can be carried out in liposomes [50] is important because it demonstrates that liposomes can resist the required temperature changes. In the light of the lipid world model it is useful to ask what catalytic functions Luisi s structures show behind direct auto catalysis. Binding of peptides to and polymerisation of amino acids in liposomes was demonstrated in various systems [51]. We are not aware of a similar effect on nucleic acid synthesis. 

Bhushan, K.R. (2006) Photolabile peptide nucleic acid monomers synthesis and photodeprotection. Synlett, (13), 2130-2132. 

Careful design was used by Seeman to prepare complementary DNA strands that self assemble into a cube with 20 nucleotide pairs along each edge. Other derivatives include nylon DNA , through the synthesis of peptide nucleic acids (PNA), and polyethylene glycol derivatized DNA. Figure 8.1 illustrates the DNA knots that can be prepared using these techniques. 

In comparison with the penicillin and cephalosporin derivatives, the peptide antibiotics are not numbered among the major antibiotics . Their action mechanisms vary, e.g. inhibition of cell-wall synthesis, increased permeability of the cell wall, or influence on nucleic acid synthesis. 

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