A Trisbenzimidazole Phosphoramidite Building Block Enables High-Yielding Syntheses of RNA-Cleaving Oligonucleotide Conjugates

The RNA cleaving catalyst tris(2-aminobenzimidazole) when attached to the 5’ terminus of oligonucleotides cuts complementary RNA strands in a highly site-specific manner. Conjugation was previously achieved by the acylation of an amino linker by an active ester of the catalyst. However, this procedure was low yielding and not reliable. Here, a phosphoramidite building block is described that can be coupled to oligonucleotides by manual solid phase synthesis in total yields around 85%. Based on this chemistry, we have now studied the impact of LNA (locked nucleic acids) nucleotides on the rates and the site-specificities of RNA cleaving conjugates. The highest reaction rates and the most precise cuts can be expected when the catalyst is attached to a strong 5’ closing base pair and when the oligonucleotide contains several LNA units that are equally distributed in the strand. However, when placed in the 5’ position, LNA building blocks tend to diminish the specificity of RNA cleavage.

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Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.9.276 ◽

2013 ◽

Vol 9 ◽

pp. 2395-2403 ◽

Cited By ~ 19

Author(s):

Felix Wojcik ◽

Sinaida Lel ◽

Alexander G O’Brien ◽

Peter H Seeberger ◽

Laura Hartmann

Keyword(s):

Double Bond ◽

Building Block ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Building Blocks ◽

Phase Synthesis ◽

Highly Efficient ◽

Monomer Sequence ◽

Full Control ◽

Block Approach

We present the solid phase synthesis of carbohydrate-functionalized oligo(amidoamines) with different functionalization patterns utilizing a novel alphabet of six differently glycosylated building blocks. Highly efficient in flow conjugation of thioglycosides to a double-bond presenting diethylentriamine precursor is the key step to prepare these building blocks suitable for fully automated solid-phase synthesis. Introduction of the sugar ligands via functionalized building blocks rather than postfunctionalization of the oligomeric backbone allows for the straightforward synthesis of multivalent glycoligands with full control over monomer sequence and functionalization pattern. We demonstrate the potential of this building-block approach by synthesizing oligomers with different numbers and spacing of carbohydrates and also show the feasibility of heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides.

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The active ester N-fmoc-3-O-[Ac4-α-D-Manp-(1→2)-Ac3-α-D-Manp-1-]=thre-O-Pfp as a building block in solid-phase synthesis of an o-linked dimannosyl glycopeptide.

Tetrahedron Letters ◽

10.1016/s0040-4039(00)97224-1 ◽

1990 ◽

Vol 31 (48) ◽

pp. 6991-6994 ◽

Cited By ~ 40

Author(s):

Anita Ma. Jansson ◽

Morten Meldal ◽

Klaus Back

Keyword(s):

Building Block ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Phase Synthesis ◽

Active Ester

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Development of Strategies for Glycopeptide Synthesis: An Overview on the Glycosidic Linkage

Current Organic Chemistry ◽

10.2174/1385272824999200701121037 ◽

2020 ◽

Vol 24 (21) ◽

pp. 2475-2497

Author(s):

Andrea Verónica Rodríguez-Mayor ◽

German Jesid Peralta-Camacho ◽

Karen Johanna Cárdenas-Martínez ◽

Javier Eduardo García-Castañeda

Keyword(s):

Chemical Synthesis ◽

Solid Phase ◽

Building Blocks ◽

Heterogeneous Environments ◽

Phase Synthesis ◽

Low Concentrations ◽

Biological Sources ◽

Synthetic Routes ◽

The Impact ◽

Potential Use

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

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Automated solid-phase synthesis of oligosaccharides containing sialic acids

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.11.69 ◽

2015 ◽

Vol 11 ◽

pp. 617-621 ◽

Cited By ~ 20

Author(s):

Chian-Hui Lai ◽

Heung Sik Hahm ◽

Chien-Fu Liang ◽

Peter H Seeberger

Keyword(s):

Sialic Acid ◽

Building Block ◽

Solid Phase Synthesis ◽

Solid Phase ◽

Sialic Acids ◽

Phase Synthesis ◽

Glycosyl Phosphate

A sialic acid glycosyl phosphate building block was designed and synthesized. This building block was used to prepare α-sialylated oligosaccharides by automated solid-phase synthesis selectively.

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