Based on our expertise and platform, CD Formulation offers a variety of base modification nucleic acid services and customizes experimental plans for our clients. Our nucleic acid base modification capabilities enhance the binding affinity and nuclease stability of nucleic acid molecules.

Overview of Base Modifications

Base-based modification of nucleic acids can be accomplished by introducing various chemical groups into their molecular structure through chemical synthesis techniques. For instance, different functional groups can be introduced at specific positions via chemical reactions such as esterification, substitution, and oxidation. Another strategy involves adding a specific chemical functional group to the starting molecule and subsequently using chemical reactions to convert it into the desired modifying group. These modifications can alter properties such as solubility, stability, and affinity of nucleic acids, ultimately enhancing the efficacy and bioavailability of nucleic acid drugs.

Fig.1 Major internal base modifications found in mRNAs. (Chanfreau G F., 2017)

Explore Our Base Modification Services

Inosine Modification Services

The inosine modification service is a technology that targets specific modifications to RNA molecules by introducing chemical groups at the inosine position. This process aims to enhance the stability and functionality of RNA.

N-Coupling Modification Services

N-alkylation modification involves introducing alkyl groups into the nitrogen atom of nucleobases through nucleophilic substitution reactions. For instance, reacting with bases, we use alkyl halides or alkyl lithium as alkylating agents to connect alkyl groups to the nitrogen atom of the base. The N-allylation reaction employs a basic catalyst to facilitate the addition reaction between allylic reagents and the base, resulting in N-allylated modifications.

Azo Modification Services

The base-specific Azo modification service is a specialized technique for RNA molecules, where we introduce Azo groups at specific bases within the RNA sequence to enhance the molecule's stability or functionality. This service typically includes sample preparation, modification design, chemical reaction implementation, purification, and quality analysis.

2'-O-Methyl RNA Base Modification Services

2'-O-Methyl RNA base modification is a specific chemical alteration of nucleic acids. This modification occurs naturally in tRNA and other RNA molecules. The addition of 2'-O-Methyl groups to a tailored oligonucleotide alters its chemical structure, thereby affecting its properties and functions. To incorporate a 2'-O-Methyl modification into an RNA sequence, simply prefix the base with a lowercase  mA, mG, mC, or mU.

2'-Methoxyethyl (2'-MOE) Modification Services

As a method of base modification, 2'-MOE includes four aspects: 2-MethoxyEthoxy A, 2-MethoxyEthoxy T, 2-MethoxyEthoxy G, and 2-MethoxyEthoxy MeC.

Affinity-Plus Base Modification Services

Affinity Plus modification of bases corresponds to locked nucleic acids (LNA). This is a modified RNA monomer that involves a methylene bridge connecting the 4' carbon and 2' oxygen of the ribose ring. Adding locked nucleic acid monomers helps increase the melting temperature of the sequence, and these bases also enhance nucleic acid resistance in vitro and in vivo.

Fluoro Base Modification Services

Highly electronegative fluorine atoms can replace the 2'-OH group of ribose, resulting in a C3'-endo (RNA-type) conformation of the 2'-F-ribonucleoside ring in oligonucleotides. The characteristics of fluoro base modifications make them particularly suitable for the design of efficient siRNAs. Fluorine modifications increase the affinity of the modified siRNA guide strand for its target RNA and enhance the stability of the siRNA duplex.

General Workflow for Base Modification

Fig.2 Flow chart of base modification. (CD Formulation)

• Sample Preparation

Customers provide the nucleic acid samples, ensuring they meet the required purity and concentration standards.

• Modification Design

Develop a tailored modification plan, selecting appropriate chemical groups and modification methods based on the customers' requirements.

• Chemical Modification

Implement the designed modifications using various chemical reactions to introduce specific functional groups at designated positions.

• Purification and Analysis

Purify the modified nucleic acids using techniques such as HPLC or desalting, followed by quality assessment through MS and other analytical methods.

• Delivery of Results

Provide clients with the modified nucleic acid samples along with detailed analytical reports, including information on modification efficiency and purity.

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Advantages of Our Base Modification Services

• Highly Customizable - We offer customized products in specifications ranging from 0.5 to 10 OD.
• High Stability - We employ specialized preparation processes to prevent degradation that could lead to the loss of modified groups.
• Diverse Purification Methods - Choose from four purification methods, including desalting and HPLC.
• Quality Control - We utilize techniques such as MS and HPLC for finished product testing.

Published Data

CD Formulation provides comprehensive customized nucleic acid and base modification services. Our biosynthesis and bioanalysis experts can help you design synthesis pathways as needed and provide analytical services for the final products. If you are interested in our services, please feel free to contact us for more details.