Can we produce nucleoside analogs with non-standard backbones or modifications?

Yes, our technology is particularly well-suited for this. The use of H-phosphonate intermediates allows us to synthesize a wide range of DNA analogs that are not easily accessible through traditional phosphoramidite chemistry.

What is the typical lead time for a custom order?

The lead time is dependent on the complexity and scale of the project. We will provide a clear and realistic timeline during our initial consultation to ensure your project stays on schedule.

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Nucleoside-based Production Service

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Characterization of Nucleosides

A nucleoside is an organic molecule that is made up of a nitrogenous base and a sugar molecule. The sugar within a nucleoside can be either ribose or deoxyribose, which is attached by glycoside bonds to the nitrogen-containing base. It can be thought of as a nucleotide that has no phosphate group. Nucleosides are important parts of DNA and RNA and play a crucial role in the storage and transmission of genetic information. Nitrogenous bases in nucleosides can be one of a few types, including adenine (A), guanine (G), cytosine (C), thymine (T), and uracil (U). A particular composition of nitrogen-containing bases and sugar molecules determines the type of nucleoside. Nucleosides play an essential role in cellular functions. They are engaged in DNA copying, transcription, and translation, which are vital for the storing and expression of genetic information. Nucleosides also have other functions in cell signaling and metabolism.

Key Technologies

We employ advanced chemical synthesis and purification techniques to produce diverse sugar-nucleosides. Its core innovation is a novel method utilizing 2'-deoxyribonucleoside 5'-phosphites as monomer units, fundamentally differing from traditional phosphoramidite/H-phosphonate approaches.

A key advancement is the use of base-unprotected 2'-deoxyribonucleoside 5'-phosphites. This eliminates complex nucleobase protection/deprotection steps, streamlining synthesis while boosting efficiency and reducing side reactions. These monomers are synthesized in a simple, one-step reaction from parent nucleosides.

The synthetic cycle involves robust chain elongation: the monomer's 3'-OH group condenses with the growing oligomer's 5'-terminal H-phosphonate monoester. Critical to this cycle is the rapid, quantitative removal of phosphite protecting groups to regenerate the H-phosphonate monoester for subsequent condensations.

This methodology enables the synthesis of diverse sugar-nucleosides and analogs, providing a versatile platform for clients.

Nucleoside-based Production Service at CD BioGlyco

There are many different types of nucleosides, and CD BioGlyco offers nucleosides production services that include, but are not limited to:

Nucleoside-based Nitrogenous Base Production Service

Fig.1 Structure of the base. (Wikipedia)

Nitrogenous bases are the essential components of nucleosides. At CD BioGlyco, we offer nucleoside production services on adenine, cytosine, guanine, uracil, and thymine. We have both biological and chemical routes to choose from in the production of nitrogenous bases, and we offer custom production solutions to each of our clients.

Nucleoside-based Ribonucleoside Production Service

Ribonucleosides play an important role in living organisms and are part of RNA. CD BioGlyco offers ribonucleoside-based production of adenosine, cytosine, guanosine, uridine, and 5-methyluridine. We have multiple routes for each riboside and are constantly optimizing our production solutions to ensure the most efficient production for our clients.

Nucleoside-based Deoxyribonucleoside Production Service

Fig.3 (Wikipedia)

Another part of nucleosides is deoxyribonucleoside, which is also a component of DNA. At CD BioGlyco, we offer services in the production of deoxyadenosine, deoxyguanosine, thymidine, uridine, and deoxycytidine. During the production process, we provide our clients with the most suitable production solution.

Nucleoside-based Derivative Production Service

Nucleoside-based derivatives of nucleosides are also important for the human body. For this reason, we also offer nucleoside-based derivative production services.

Workflow

Our sugar-nucleoside production service is designed as a collaborative and efficient process to ensure the highest quality results for your project.

Project Consultation and Design

The process starts with a detailed consultation with our expert scientific team. We work with you to define your specific needs, including the exact structure of the sugar-nucleoside, desired quantity, and purity requirements. We then design a custom synthesis plan to meet these specifications.

Monomer Unit Synthesis

We begin by preparing the necessary monomer units, employing a simple one-step reaction from base-unprotected 2'-deoxyribonucleosides. For nucleosides that are less soluble, like 2'-deoxycytidine and 2'-deoxyguanosine, we use co-solvents such as N-methylpyrrolidone (NMP) with pyridine to significantly improve solubility and enhance reaction selectivity.

Chain Elongation and Synthesis

This stage involves the sequential addition of monomer units to build the target sugar-nucleoside or oligonucleotide. Our chain elongation cycle includes three key steps: deprotection, condensation, and capping. The use of H-phosphonate intermediates enables the synthesis of a wide variety of DNA analogs that are not accessible via other methods.

Purification and Quality Assurance

After synthesis, the crude product undergoes a rigorous purification process. We leverage advanced chromatographic techniques, and in some cases, the monomer units can be easily purified by crystallization. Each batch is then subjected to a comprehensive quality control assessment, including NMR, HPLC, and mass spectrometry, to confirm its identity, structure, and purity.

Final Product Delivery

The high-purity, quality-controlled sugar-nucleoside is delivered with a detailed certificate of analysis (CoA), providing you with complete confidence in the product's quality and specifications.

Our workflow. (CD BioGlyco)

Publication Data

DOI.: 10.3390/molecules27113499

Journal: Molecules

IF: 4.6

Published: 2020

Results: This study synthesized seven modified sugar and nucleoside analogs (compounds 2-8) from α-D-glucose through a 21-step pathway. The compounds were evaluated for analgesic activity in mice using acetic acid-induced writhing assays and for cytotoxicity against HeLa cancer cells via trypan blue exclusion and CCK-8 assays. Key findings include:

Compounds 2, 7, and 8 significantly reduced writhing by 56%, 62%, and 63%, respectively, indicating potent peripheral analgesia.
Compound 6 exhibited notable cytotoxicity with an IC₅₀ of 54 µg/mL against HeLa cells.Molecular docking revealed that analgesic compounds 2, 7, and 8 bind strongly to cyclooxygenase-1/2 (COX-1/2) and adenosine kinase, suggesting dual inhibition pathways. Cytotoxic compound 6 showed high affinity for cancer targets like cytidine deaminase, tyrosine-protein kinase Src, and thymidine kinase 1. This work presents the first report of compound 8's synthesis/analgesia and compound 6's anticancer potential, highlighting their therapeutic promise.

Application

Nucleic Acid-Based Therapeutics

Our nucleosides are used in the synthesis of antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and aptamers for targeted gene regulation and therapeutic intervention.

Antiviral and Anticancer Drug Discovery

Many antiviral and anticancer drugs are nucleoside analogs, and our service is critical for the research of these therapeutic agents.

Genetic and Epigenetic Research

Modified nucleosides are vital tools for studying DNA and RNA structure, function, and epigenetic modifications, offering insights into gene expression and disease mechanisms.

Advantage

Our method uses base-unprotected nucleoside phosphites as monomer units, which simplifies the overall synthetic process. This innovative approach eliminates the need for complex protection and deprotection steps, making the synthesis faster and more efficient.
We have optimized our one-step reaction to synthesize monomer units in good yields, and these compounds can be readily purified by crystallization.
The H-phosphonate intermediates generated by our method are highly versatile and serve as excellent precursors for synthesizing a wide range of DNA analogs that are challenging to obtain through conventional phosphoramidite chemistry.

Frequently Asked Questions

Associated Services

Our nucleoside production services provide high-purity molecular building blocks (adenine, cytosine, guanine, uracil, thymine) essential for synthesizing oligonucleotide therapeutics. To transform these nucleosides into functionally advanced constructs, we offer precision Oligonucleotide Modification Services that enhance stability, targeting, and therapeutic efficacy:

CD BioGlyco is a company with extensive experience in the manufacturing of nucleosides and their derivatives. Our versatile analytical platform and specialized researchers provide custom production services. If you are interested in our services, please do not hesitate to contact us.

Reference

Hussain, F.; et al. Synthesis of sugar and nucleoside analogs and evaluation of their anticancer and analgesic potentials. Molecules. 2020, 27(11): 3499. (Open Access)