Browse
Submit Data
Databases
API
Help

Dataset Information

32 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Novel Convenient Approach to the Solid-Phase Synthesis of Oligonucleotide Conjugates.

ABSTRACT: A novel and convenient approach for the solid-phase 5'-functionalization of oligonucleotides is proposed in this article. The approach is based on the activation of free 5'-hydroxyl of polymer support-bound protected oligonucleotides by N,N'-disuccinimidyl carbonate followed by interaction with amino-containing ligands. Novel amino-containing derivatives of closo-dodecaborate, estrone, cholesterol, and ?-tocopherol were specially prepared. A wide range of oligonucleotide conjugates bearing closo-dodecaborate, short peptide, pyrene, lipophilic residues (cholesterol, ?-tocopherol, folate, estrone), aliphatic diamines, and propargylamine were synthesized and characterized to demonstrate the versatility of the approach. The developed method is suitable for the conjugate synthesis of oligonucleotides of different types (ribo-, deoxyribo-, 2'-O-methylribo-, and others).

SUBMITTER: Meschaninova MI

PROVIDER: S-EPMC6930482 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Novel Convenient Approach to the Solid-Phase Synthesis of Oligonucleotide Conjugates.

Meschaninova Mariya I MI Novopashina Darya S DS Semikolenova Olga A OA Silnikov Vladimir N VN Venyaminova Alya G AG

Molecules (Basel, Switzerland) 20191122 23

A novel and convenient approach for the solid-phase 5'-functionalization of oligonucleotides is proposed in this article. The approach is based on the activation of free 5'-hydroxyl of polymer support-bound protected oligonucleotides by N,N'-disuccinimidyl carbonate followed by interaction with amino-containing ligands. Novel amino-containing derivatives of closo-dodecaborate, estrone, cholesterol, and α-tocopherol were specially prepared. A wide range of oligonucleotide con ...[more]

PMID: 31771111

Similar Datasets

A Versatile Solid-Phase Approach to the Synthesis of Oligonucleotide Conjugates with Biodegradable Hydrazone Linker.

Project description:One of the ways to efficiently deliver various drugs, including therapeutic nucleic acids, into the cells is conjugating them with different transport ligands via labile or stable bonds. A convenient solid-phase approach for the synthesis of 5'-conjugates of oligonucleotides with biodegradable pH-sensitive hydrazone covalent bonds is proposed in this article. The approach relies on introducing a hydrazide of the ligand under aqueous/organic media to a fully protected support-bound oligonucleotide containing aldehyde function at the 5'-end. We demonstrated the proof-of-principle of this approach by synthesizing 5'-lipophilic (e.g., cholesterol and α-tocopherol) conjugates of modified siRNA and non-coding RNAs imported into mitochondria (antireplicative RNAs and guide RNAs for Mito-CRISPR/system). The developed method has the potential to be extended for the synthesis of pH-sensitive conjugates of oligonucleotides of different types (ribo-, deoxyribo-, 2'-O-methylribo-, and others) with ligands of different nature.

| S-EPMC8067880 | biostudies-literature

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics.

Project description:An efficient solid-phase-supported peptide synthesis (SPPS) of morpholinoglycine oligonucleotide (MorGly) mimics has been developed. The proposed strategy includes a novel specially designed labile linker group containing the oxalyl residue and the 2-aminomethylmorpholino nucleoside analogues as first subunits.

| S-EPMC4077379 | biostudies-literature

Convenient Synthesis of Acetonide Protected 3,4-Dihydroxyphenylalanine (DOPA) for Fmoc Solid-Phase Peptide Synthesis.

Project description:We report a facile approach to the synthesis of acetonide and Fmoc protected 3,4-dihydroxyphenylalanine (DOPA), Fmoc-DOPA(acetonide)-OH. By protecting the amino group of DOPA with a phthaloyl group and the carboxyl group as a methyl ester, acetonide protection of the catechol of DOPA derivative was realized in the presence of p-toluenesulfonic acid. Following removal of protecting groups, the intermediate was converted to Fmoc-DOPA(acetonide)-OH, which was successfully incorporated into a short DOPA-containing peptide, derived from marine tubeworm cement proteins Pc1 and Pc2.

| S-EPMC2598405 | biostudies-literature

A reagent for the convenient, solid-phase synthesis of N-terminal peptide hydroxylamines for chemoselective ligations.

Project description:A new N-sulfonyloxaziridine reagent for the conversion of N-terminal peptide amines to the corresponding hydroxylamines without overoxidation or erosion of stereochemistry is described. The products are N-terminal hydroxylamines, which are substrates for chemoselective amide-bond forming reactions with alpha-ketoacids. The success of this reagent arises from covalent precomplexation with the substrate via imine bond formation followed by an intramolecular oxygen-atom transfer to the amine. An unexpected stereochemical mismatch between the racemic reagent and the chiral peptide substrates was addressed by the preparation of an enantipure version of this reagent and provides further support for the proposed mechanism.

| S-EPMC2677186 | biostudies-literature

Pyrene-nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies.

Project description:Fluorescent pyrene-linker-nucleobase (nucleobase = thymine, adenine) conjugates with carbonyl and hydroxy functionalities in the linker were synthesized and characterized. X-ray single-crystal structure analysis performed for the pyrene-C(O)CH2CH2-thymine (2) conjugate reveals dimers of molecules 2 stabilized by hydrogen bonds between the thymine moieties. The photochemical characterization showed structure-dependent fluorescence properties of the investigated compounds. The conjugates bearing a carbonyl function represent weak emitters as compared to compounds with a hydroxy function in the linker. The self-assembly properties of pyrene nucleobases were investigated in respect to their binding to single and double strand oligonucleotides in water and in buffer solution. In respect to the complementary oligothymidine T10 template in water, compounds 3 and 5 both show a self-assembling behavior according to canonical base-base pairing. However, in buffer solution, derivative 5 was much more effective than 3 in binding to the T10 template. Furthermore the adenine derivative 5 binds to the double-stranded (dA)10-T10 template with a self-assembly ratio of 112%. Such a high value of a self-assembly ratio can be rationalized by a triple-helix-like binding, intercalation, or a mixture of both. Remarkably, compound 5 also shows dual staining pattern in living HeLa cells. Confocal microscopy confirmed that 5 predominantly stains mitochondria but it also accumulates in the nucleoli of the cells.

| S-EPMC5727867 | biostudies-literature

Efficient Synthesis of 2'-O-Methoxyethyl Oligonucleotide-Cationic Peptide Conjugates.

Project description:Single-stranded phosphorothioate (PS) oligonucleotide drugs have shown potential for the treatment of several rare diseases. However, a barrier to their widespread use is that they exhibit activity in only a narrow range of tissues. One way to circumvent this constraint is to conjugate them to cationic cell-penetrating peptides (CPPs). Although there are several examples of morpholino and peptide nucleic acids conjugated with CPPs, there are noticeably few examples of PS oligonucleotide-CPP conjugates. This is surprising given that PS oligonucleotides presently represent the largest class of approved RNA-based drugs, including Nusinersen, that bears the 2'-O-methoxyethyl (MOE)-chemistry. In this work, we report a method for in-solution conjugation of cationic, hydrophobic peptides or human serum albumin to a 22-nucleotide MOE-PS oligonucleotide. Conjugates were obtained in high yields and purities. Our findings pave the way for their large-scale synthesis and testing in vivo.

| S-EPMC9291120 | biostudies-literature

Synthesis of the 5'-Se-thymidine phosphoramidite and convenient labeling of DNA oligonucleotide.

Project description:The synthesis of the 5'-Se-derivatized thymidine and phosphoramidite is reported, and the Se-phosphoramidite was incorporated into DNA. Because of its high nucleophilicity, this 5'-Se-moiety permits convenient postsynthetic modification of oligonucleotides. The proof of principle was successfully demonstrated by incorporating fluorescein into DNA. It was also found that the 5'-dye-labeled Se-DNA can be recognized by DNA polymerase as an efficient primer. This novel strategy opens a new avenue for nucleic acid probe preparation and detection.

| S-EPMC3241971 | biostudies-literature

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer.

Project description:In this article, we have successfully designed and demonstrated a novel continuous process for assembling targeting ligands, peptidic spacers, fluorescent tags and a chelating core for the attachment of cytotoxic molecules, radiotracers, nanomaterials in a standard Fmoc solid-phase peptide synthesis in high yield and purity. The differentially protected Fmoc-Lys-(Tfa)-OH plays a vital role in attaching fluorescent tags while growing the peptide chain in an uninterrupted manner. The methodology is versatile for solid-phase resins that are sensitive to mild and strong acidic conditions when acid-sensitive side chain amino protecting groups such as Trt (chlorotrityl), Mtt (4-methyltrityl), Mmt (4-methoxytrityl) are employed to synthesise the ligand targeted fluorescent tagged bioconjugates. Using this methodology, DUPA rhodamine B conjugate (DUPA = 2-[3-(1,3-dicarboxypropyl)ureido]pentanedioic acid), targeting prostate specific membrane antigen (PSMA) expressed on prostate, breast, bladder and brain cancers and pteroate rhodamine B, targeting folate receptor positive cancers such as ovarian, lung, endometrium as well as inflammatory diseases have been synthesized. In vitro studies using LNCaP (PSMA +ve), PC-3 (PSMA -ve, FR -ve) and CHO-? (FR +ve) cell lines and their respective competition experiments demonstrate the specificity of the newly synthesized bioconstructs for future application in fluorescent guided intra-operative imaging.

| S-EPMC6204756 | biostudies-literature

Chlorotrifluoroethylidenes: an efficient and convenient approach to their synthesis.

Project description:A convenient one step synthesis of chlorotrifluoroalkyl olefins starting from aldehydes was developed. The stable reagent 2-((1-chloro-2,2,2-trifluoroethyl)sulfonyl)benzothiazole was prepared from readily available benzothiazole-2-thiol and halothane. This method comprises using stable 2-((1-chloro-2,2,2-trifluoroethyl)sulfonyl)benzothiazole according to the Julia procedure and presents new opportunities for the synthesis of trifluoroalkylidene derivatives.

| S-EPMC9053503 | biostudies-literature

A new approach to amplified telomerase detection with polyvalent oligonucleotide nanoparticle conjugates.

Project description:We report a new assay for human telomerase activity that relies on polyvalent oligonucleotide nanoparticle conjugates as diagnostic probes and amplification units. Gold nanoparticles functionalized with specific oligonucleotide sequences can efficiently capture telomerase enzymes and subsequently be elongated. Both the elongated and unmodified oligonucleotide sequences are simultaneously measured. The two strands not only serve as internal positive controls for each other but also provide a way of amplifying signal. At high concentrations, both elongated and unmodified strands exhibit measurable responses. At low telomerase concentrations (e.g., from 10 HeLa cells), elongated strands cannot be detected, but the unmodified sequences, which come from the same probe particles, can be detected because their concentration is higher, providing a novel form of amplification. This new assay rivals the sensitivity of the conventional PCR-based method of telomerase detection.

| S-EPMC8191123 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data