Synthesis of Spirannic Nucleosides and Their Incorporation into Oligonucleotides

Abstract

The spirannic nucleosides dH _α, dH _β, sB and cB were synthesized and incorporated into oligonucleotides using the cpg-oxalyl solid support strategy.     

A Novel Approach for the Synthesis of seco C-Nucleoside Analogues

Abstract

The synthesis of 4-amino-3-(D-gluco- or D-galacto-pentitol-1.yl)-5-mercapto-1,2,4-triazoles and their conversion to the respective 6-methyl-3-(1,2,3,4,5-penta-O-acetyl-pentitol-1-yl)1,2,4-triazolo[3,4-b]1,3,4-thiadiazoles have been achieved. The vicinal coupling constants were used to deduce the favored conformations.     

Straightforward Synthesis of 6-Thiodeoxyguanosine and Its Incorporation into Oligodeoxynucleotides

Abstract

A convenient synthesis of 6-thiodeoxyguanosine from deoxyguanosine is described. Simple methods for incorporating 6-thiodeoxyguanosine into oligodeoxynucleotides are also given.     

Straightforward Synthesis of 6-Thiodeoxyguanosine and Its Incorporation into Oligodeoxynucleotides

Abstract

A convenient synthesis of 6-thiodeoxyguanosine from deoxyguanosine is described. Simple methods for incorporating 6-thiodeoxyguanosine into oligodeoxynucleotides are also given.     

Synthesis of Novel Representatives of Phosphoryl Guanidine Oligonucleotides

Russian Journal of Bioorganic Chemistry - Novel representatives of phosphoryl guanidine oligonucleotide derivatives were prepared in this study. A synthetic scheme has been proposed and implemented...     

Incorporation of Antisense Oligonucleotides into Lipophilic Concatemeric Complexes Provides Their Effective Penetration into Cells

Russian Journal of Bioorganic Chemistry - The development of highly effective molecular and biological tools to facilitate the penetration of therapeutic nucleic acids into cells opens a direct way...     

Chemical Incorporation of 1-Methyladenosine,Minor tRNA Component,into Oligonucleotides

Abstract

The synthesis of suitably protected 1-methyladenosine derivatives has been developed and its successful chemical incorporation into oligonucleotides was achieved.     

Synthesis and Triplex Binding Properties of Oligonucleotides Containing a Novel Nucleobase

Abstract

The thiazolo-indole compound 1 bearing the complementary donor-acceptor-donor sites (dad) was designed for specific recognition of an AT inverted base pair in pyrimidine triple helix motif. It was successfully incorporated into 14-mer oligonucleotide using a serinol unit as sugar derivative. The triple helix hybridization studies were examined by means of thermal denaturation experiments with a 26-mer DNA duplex containing the AT inverted base pair.     

Glycal Ethers as Starting Materials in C-Nucleoside Synthesis

Abstract

When 3,4,6-tri-O-benzyl-g-glucal (3) is treated with thallium (III) nitrate, trihydrate in acetonitrile, 2,5-anhydro-3,4,6-tri-O-benzyl-D-mannose (4), a precursor of the showdomycin analogue (5), is obtained. Ring-contraction of (3) can also be effected by a three-step process [(i) PhSeCl, tetrahydrofuran, (ii) Et₃N, H₂O; (iii) 3-ClC₆-H₄CO₃H, KeOH]. Other examples of these ring-contraction reactions are described.     

Incorporation of Shikimic Acid into Corynecins and Its Regulation

In the biosynthesis of corynecins by Corynebacterium hydrocarboclastus, it appeared that shikimic acid was one of the efficient precursors, where shikimic acid-U-¹⁴C was incorporated into corynecins in the yield of approximately 15%. Analyses of degradation products of labeled corynecins demonstrated that shikimic acid was incorporated specifically into aromatic ring of corynecins.

The incorporation of shikimic acid was inhibited by several aromatic amines such as p-aminophenylserinol-N-propionamide, although the uptake of shikimic acid was not affected, suggesting that biosynthesis of corynecins might be regulated by p-aminophenyl intermediates. Furthermore, p-ammophenylethylalcohol was found to be a potent inhibitor of biosynthesis of corynecins. In contrast, corynecins and other p-nitro-phenyl derivatives, aromatic amino acids and vitamins related to shikimic acid pathway did not inhibit the biosynthesis of corynecins from shikimic acid.     

A New,Efficient Exocyclic Amine Protection Scheme for 2-Aminoadenosine and Derivatives for Incorporation into Oligonucleotides

Abstract

We introduce a novel approach to incorporate 2-aminoadenosine into oligonucleotides in which 2-fluoroadenosine and its derivatives are used to prepare the monomers and, under normal oligonucleotide deprotection conditions, is converted to the desired 2-aminoadenosine and derivatives.     

Synthesis of Thymine-Modified Oligonucleotides

Abstract

Oligonucleotide-resins containing N-nitrothymidine residues yield N3-thymine modified oligonucleotides by reaction with a variety of amines followed by the standard ammonia treatment.     

Synthesis and Assembly of Simian Virus 40 II. Synthesis of the Major Capsid Protein and Its Incorporation into Viral Particles

African green monkey kidney cells infected by simian virus 40 were analyzed for the presence of the major capsid protein (capsid protein I) by immunological and radiolabeling techniques. Antisera with different specificities were prepared by immunization with intact or denatured viral particles. Antisera prepared against intact virus reacted by complement fixation with viral particles and with an 8S subunit containing the capsid protein I. Antisera prepared against denatured viral particles reacted with unassembled capsid protein(s) as well as with viral particles. These antisera were used to detect 8S viral subunits or unassembled viral capsid protein in soluble extracts of infected cells after centrifugation at 100,000 x g to remove viral particles. The soluble antigen pool was found to be small during infection with wild-type virus or a temperature-sensitive mutant deficient in the synthesis of viral particles. Pulse-chase experiments, performed at a high multiplicity of infection, also indicated a small pool of nonparticle capsid protein I. Radioactive lysine was incorporated into capsid protein I of virus particles during a 2-hr pulse. A subsequent chase with excess unlabeled lysine resulted in only a slight increase in the radio-activity found in capsid protein I of viral particles. Furthermore, in the same experiments, capsid protein I was incorporated preferentially into empty shells during the pulse with a shift in radioactivity to intact virions during the chase period, indicating a possible precursor relationship between the two types of virus particles.     

Evaluation of Oligonucleotides with Novel Modifications

Abstract

Oligodeoxynucleotides modified with carboxamide linked dimeric nuclcotides and an acyclic nucleoside were prepared and investigated for their hybridization properties toward DNA.     

Incorporation of C-Leucine into Apple Leaf Protein and Its Inhibition by Protein Synthesis Inhibitors during Growth and Senescence

Of the total ¹⁴C-leucine taken up by intact apple (Pyrus malus L., Golden Delicious) leaf discs, 44 to 62% is incorporated into protein from June to early October. Of this amount, an average of 35% is released by mild, room temperature acid hydrolysis. Prior to mid-August when leaf protein begins to decline, 15 to 20% of the ¹⁴C-leucine incorporated into protein occurs in water-(buffer) soluble protein, of which only 3% is released by mild acid hydrolysis. After mid-August, 40% of the label in protein occurs in soluble protein. The specific radio-activity of the soluble protein increases by 4- to 5-fold after mid-August, while that of total protein increases by less than 2-fold. In presenescent leaves (before the decline of protein in August) 20 micrograms per milliliter cycloheximide inhibits the incorporation of ¹⁴C-leucine into protein by 71%, and 20 micrograms per milliliter chloramphenicol inhibits it by 30%. In senescing leaves, cycloheximide inhibits ¹⁴C-leucine by 85% or more, while chloramphenicol inhibits it by less than 15%. Coincident to the initial decline of leaf protein, chloramphenicol greatly loses its ability to inhibit the incorporation of ¹⁴C-leucine into apple leaf protein. At all leaf ages, chloramphenicol increases the loss of chlorophyll from apple leaf discs. The effect of cycloheximide on leaf disc senescence changes with leaf age: in early season samples, it increases the loss of chlorophyll; in mid-season samples, it has no effect; and in late season samples, it retards the loss of chlorophyll.     

Three-phase - Synthesis of Oligonucleotides

Abstract

Stable reagents were made from nucleoside-phospho-rochloridites and polymeric sec. amines. Treatment of these with tetrazole/CH₃CN and transfer of the resulting solution to immobilized oligonucleotide gave 95% chain elongation.     

Solid-Phase Synthesis of Modified Oligonucleotides

Synthetic oligonucleotides are ubiquitously found in most laboratories since solid-phase synthesis protocols have become highly optimized. These protocols make it possible to synthesize a large variety of modified oligonucleotides. As one example, we will review some of the developments regarding oligonucleotide synthesis from our own group. In particular, we will describe the synthesis of oligonucleotides carrying non-natural bases, of oligonucleotide–peptide conjugates, and of modified oligonucleotides used in the assembly of nanomaterials. This work is dedicated to the memory of Bruce Merrifield.     

DNA Conjugates as Novel Functional Oligonucleotides

Abstract

Oligodeoxynucleotides with RNA cleavage activity 1) were conjugated with amines and peptides by solid phase fragment condensation (SPFC). It was found that 29 mer DNA enzyme conjugated with spermine at its 5′-end showed higher affinity to the target RNA sequence and 40 times higher activity of cleavage than native DNA enzyme. It is also to be noted that conjugate DNA enzymes showed increased resistance against nuclease digestion     

Glycerol-Furcated Oligonucleotides: Synthesis and Aggregation

Abstract

The synthesis of the bi-furcated complementary oligonucleotides 2 and 3 is described and their complex formation is studied as a function of their molar ratio and ionic strength by means of temperature-dependent UV- and CD spectroscopy as well as by dynamic light scattering. Structural proposals for the different aggregates are given.     

Amino Acid Nucleic Acids: Synthesis and Hybridization Properties of a Novel Class of Antisense Oligonucleotides

Abstract

Oligonucleotides containing novel phoshoramidite 12 were synthesized and studied for their hybridization properties for the first time. Interestingly, these modified oligonucleotides showed a remarkable resistance to exonuclease.