Classification of Base-based N-conjugation Modification

N-conjugate modification of nucleosides and nucleotides generally refers to the introduction of a conjugated structure by modifying the nitrogen atom in the base. Common N-conjugate modification reactions include N-alkylation, N-arylation, and N-allylation. N-alkylation modifications are formed by introducing an alkyl group to the nitrogen atom of the nucleoside base through nucleophilic substitution reactions. For example, the alkyl group is attached to the nitrogen atom of the base using an alkylophilic reagent (e.g., alkyl halide or alkyl lithium) in a reaction with the base. The N-arylation reaction is similar to the N-alkylation reaction in that an aryl group is introduced via a nucleophilic substitution reaction. The N-allylation reaction utilizes a base catalyst to catalyze an addition reaction between an allyl reagent and the base, thereby introducing an allyl group to the nitrogen atom of the base, resulting in a modification that is N-allylated.

Fig.1 General approach of the abiotic organic synthesis of canonical nucleosides and nucleotides. (Yadav, et al., 2020)

Base-based N-conjugation Modification Service at CD BioGlyco

CD BioGlyco has successfully established a Glyco™ Synthesis Platform to provide clients with a complete Custom Sugar-nucleotides Synthesis Service. Our professional nucleoside & nucleotide Modification Service and Oligosaccharide Modification Service have received wide recognition in the field of glycochemistry. The details of our base-based N-conjugation modification are as follows:

• Protection of hydroxyl groups
  The hydroxyl group would be protected to prevent it from unintended chemical reactions during the reaction. Commonly used protecting groups include silyl groups such as tert-butyldimethylsilyl, ester groups, and acetyl groups. We will select the appropriate protecting group according to the specific experimental conditions and the type of modification required.
• Modification process
  We will introduce the desired functional groups using appropriate modification reagents such as alkyl halides, aryl halides, alkyl lithium, aryl lithium, etc., depending on the specific type of modification. The selectivity of the reaction is controlled and determine the appropriate reaction conditions by conducting small trials in advance based on the modifying reagent and reaction type.
• Deprotection and structural analysis
  After completion of the N-conjugation modification, the protecting group is removed to restore the structure of the nucleotide. The products were purified and structurally characterized using techniques such as nuclear magnetic resonance (NMR) and mass spectrometry (MS).

Fig.2 Flow chart of base-based N-conjugation modification. (CD BioGlyco)

Applications

• By attaching fluorescent dyes to nitrogen atoms, nucleosides or nucleotides can be used as fluorescent probes for applications such as bioimaging, molecular detection, and cell tracking.
• The introduction of a sugar functional group on the nitrogen atom of a nucleotide can be used to construct sugar-nucleic acid complexes for targeted delivery of gene drugs or preparation of biosensors.

Advantages of Us

• We are committed to providing innovative, efficient, and workable solutions to ensure that our finishing routes deliver the desired results and maximize value for our clients.
• With advanced technology and highly accurate measurement capabilities, a wide range of products can be analyzed and tested.
• We have a team of skilled problem-solving technicians. They have a wealth of professional knowledge and experience and are skilled at analyzing and solving a wide range of technical problems.

CD BioGlyco provides clients with a full range of customized nucleoside & nucleotide N-conjugation modification services based on base. Our experts in organic synthesis and glycobiology can also help you design synthetic pathways according to your needs and provide analytical services for the final product. If you are interested in our services, please feel free to contact us for more details.