Phosphitylation of Primary Carboxamides. Synthesis of Peptide-Oligonucleotide Conjugates with Acylphosphoramidate Linkages

Abstract

N-acylphosphoramidates can be obtained from the reaction of phosphitylated primary carboxamides and an alcohol in the presence of an acid catalyst such as tetrazole and subsequent oxidation. The reaction is useful for the preparation of peptide-oligonucleotide conjugates.     

Total Stepwise Solid-Phase Peptide-Oligonucleotide Conjugate Synthesis on Macroporous Polystyrene

Abstract

An efficient total stepwise solid-phase synthesis of oligonucleotide-peptide conjugates on a macroporous polystyrene is described. Extending our homoserine linker approach, we prepared a range of fluorescein-labelled conjugates containing one of two different peptides together with oligonucleotides containing 2′-deoxynucleoside or 2′-O-methylribonucleoside phosphodiesters, or gapmers containing 2′-deoxyphosphorothioate sequences flanked by 2′-O-methyl wings.     

Synthesis of Paclitaxel-BGL Conjugates

Four kinds of symmetrically branched oligoglyceryl trimeric (BGL003)-paclitaxel conjugates and a corresponding heptameric (BGL007) conjugate were synthesized. Molecular weights of all the compounds were less than two times that of paclitaxel. The anti-tumor activity of the most water-soluble BGL003 conjugate was examined and found to be preserved in spite of the chemical modification that is displacement of the N3'-debenzoyl residue with the BGL003 succinyl residue.     

Synthesis of Nucleopeptide-Oligonucleotide Conjugates

Abstract

Two nucleopeptides (NPs) were synthesized on the base of δ-ornithine peptides by modification of the α-amino ornithine functions with pyrimidyl-1- and purinyl-9-acetic acids or with pyrimidyl-1- and purinyl-9-alanines. NPs were prepared on solid polymer bearing photolinker. Conjugates with the 16-mer oligonucleotide complementary to the env AUG codon region of the Friend murine leukemia virus were prepared.     

Conformationally Restrained Chiral PNA Conjugates: Synthesis and DNA Complementation Studies

Abstract

In recent times, PNA (I), a structural mimic of DNA in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl)glycine (aeg) linkage has emerged as a potential antisense therapeutic agent.¹ A major limitation of PNAs from an application perspective is their poor solubility in aqueous medium and being achiral, they bind to cDNA in both parallel (N-PNA/5′-DNA) and antiparallel (N-PNA/3′-DNA) modes. In this connection, we have designed spermine conjugated and conformationally constrained PNA analogues to generate the 4-aminoprolyl backbone (II).² These were synthesised and evaluated for their DNA binding abilities by using UV and CD spectroscopic studies. It is seen that incorporation of one 4-aminoprolyl unit at the N-terminus of a PNA chain not only enhances the inherent binding of PNA to DNA, but also imparts significant bias in parallel and antiparallel binding with cDNA. Conjugation of spermine at C-terminus enhanced the PNA solubility.     

Synthesis of Circular Oligonucleotide Conjugates

Abstract

A new approach to the non-template synthesis of circular oligodeoxyribonucleotides containing flexible non-nucleotidic linkers has been developed. Using this technique a set of circular molecules representing triple helix forming, antisense and guanosine tetrad containing oligonucleotides has been obtained.     

Synthesis of N,N-Dialkylaniline-2′-deoxyuridine Conjugates for DNA-Mediated Electron Transfer Studies

Abstract

Syntheses of two analogs of deoxyuridine with N,N-dialkylaniline chromophores are reported. 5-[3-(N-methylphenylamino)propanoyl]-2′-deoxyuridine (1) and 5-[2-(4-N,N-dimethylaminophenyl)ethyl)]-2′-deoxyuridine (2) are prepared by palladium-mediated coupling. Preparation of 2 was facilitated by in situ transient O⁴-trimethylsilyl protection during alkynylation which suppressed secondary cyclization of the coupling adduct.     

肽缀合反义寡核苷酸的合成和性能

反义寡核苷酸可作为基因表达的抑制剂和潜在的治疗药物,但多种类型的寡核苷酸为聚阴离子化合物,难以跨过细胞膜.已知包括融合肽、信号肽在内的多种生物活性多肽具有跨膜与核定位能力.讨论了反义寡核苷酸-肽缀合物的合成和生物活性.     

薯蓣皂甙元ELISA定量分析方法的建立Ⅰ-薯蓣皂甙元全抗原的合成

建立薯蓣皂甙元的ELISA定量分析方法必须先合成薯蓣皂甙元的全抗原。试验利用薯蓣皂甙元3位上的-OH,在DMAP的催化下,薯蓣皂甙元与丁二酸酐反应,生成薯蓣皂甙元丁二酸单酯,用MSI、R1、H NMR1、3CNMR等方法对产物结构进行了表征。用混合酸酐法制备薯蓣皂甙元与牛血清白蛋白的结合物(DG-HS-BSA),碳二亚胺法制备薯蓣皂甙元与卵清蛋白的结合物(DG-HS-OVA),经TNBS测定,每分子结合物连接的薯蓣皂甙元分子数分别为28.0和8.8。     

Thermodynamic Melting Studies on Oligonucleotide-Peptide Conjugates

Abstract

A small library of oligonucleotide-peptide conjugates has been prepared and studied to explore the influence of the various peptide side chain (cationic, anionic or hydrophobic) on the hybridation properties of the DNA.     

Studies Towards the Synthesis of Medermycin via Dötz Benzannulation

The C‐arylglycosides are available in enantiomerically pure form via the Dötz benzannulation reaction between Fischer alkenyl chromium carbene complexes and alkynes; it also could be converted to a precursor of medermycin by O‐carbamate directed ipso bromination and nitrile substitution in good overall yields. Chirality 27:18–22, 2015. © 2014 Wiley Periodicals, Inc.     

Studies Towards Synthesis of Dinucleoside Arylphosphonates with Metal Complexing Properties

Abstract

An efficient and stereospecific synthesis of dinucleoside 4′-(2,2′:6′,2″-terpyridyl)phosphonate 2 and 5-(2,2′-bipyridyl)phosphonate 3 via a palladium(0) cross coupling strategy has been developed.     

Studies Towards the Synthesis of the Saturated and Unsaturated Carbocyclic Methylene Phosphonate Analogs of Dideoxyadenosine

Abstract

The synthesis of the saturated carbocyclic methylene phosphonate analog of ddAMP is described by two different methods (epoxyde opening and “purinoselenylation”). Studies towards the formation of 2′,3′ unsaturated analogs by selenoxyde or mesylate elimination are also reported.     

Tri-N-Boc-Tetraazamacrocycle-Nucleoside Conjugates: Synthesis and anti-HIV activities

Abstract

As far as linear N-Boc-polyamines conjugates elicited remarkable anti-HIV activity, the synthesis and anti-HIV properties of cyclic N-Boc-polyamines conjugates such as tetraazamacrocycle-nucleoside were studied. These new conjugates include an ester linkage between the two moieties. They were synthesized using Benzotriazol-l-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate coupling reagent, in the case of N-alkyl polyazamacrocycle derivatives, or through direct condensation of the acyl chloride derivative with nucleoside in the case of N-acyl polyazamacrocycle compounds. None of the new conjugates presented anti-HIV activity greater than that of the corresponding parent nucleosides.     

Synthesis and Hybridization Characteristics of Oligodeoxynucleotide-Alkaline Phosphatase Conjugates

Abstract

Modified oligodeoxynucleotides, 20 to 30 bases in length and containing “linker arm” bases, are chemically synthesized, then attached covalently to alkaline phosphatase in a 1:1 conjugate through a 19 atom spacer. Such conjugates hybridize rapidly and selectively to complementary sequences similar to unmodified oligomers, and allow colorimetrlc and fluorogenic detection of hybrids.     

Synthesis and Analytical Characterization of RNA-Polyethylene Glycol Conjugates

Abstract

Polyethylene glycols with degrees of polymerization from 5 to more than 100 were incorporated into synthetic oligoribonucleotides by automated solid phase synthesis at 3′-terminal, 5′-terminal and internal positions. The conjugates were characterized by chromatographic, electrophoretic and mass-spectrometric methods. The influence of coupling site, polymer size and number of coupled polymers per oligonucleotide on the molecular properties of the conjugates is investigated.     

NMR Studies of the MDP Conjugates with Amino-Acridine/Acridone Derivatives

¹H and ¹³C NMR studies allowed us to determine the structure of anticancer active MDP analogs modified at the C-terminus with amino-acridine/acridone derivatives. The products contain an isoglutamine residue without contamination by their isomers containing a glutamine residue as could be expected based on the literature data.     

NMR Studies of the MDP Conjugates with Amino-Acridine/Acridone Derivatives

Summary ¹H and¹³C NMR studies allowed us to determine the structure of anticancer active MDP analogs modified at the C-terminus with amino-acridine/acridone derivatives. The products contain an isoglutamine residue without contamination by their isomers containing a glutamine residue as could be expected based on the literature data.     

Synthesis of Oligonucleotide Conjugates with the Aid of N-Chloroacetamidohexyl Phosphoramidite Reagent

Abstract

A novel phosphoramidite building block derived from N-chloroacetyl-6-aminohexanol is attached at the 5′-terminus on the last step of oligonucleotide synthesis. Postsynthetic treatment of support-bound modified oligonucleotides with a variety of amines and mercaptanes affords oligonucleotide conjugates in a high yield.