The Role of P-N Bond in Drug Development

The phosphate ester bond (P-O bond), a common linkage structure in conventional drug design, is widely used to construct active molecules and drug-candidate compounds. However, the introduction and substitution of P-N bonds can offer a range of advantages and potential pharmacological benefits. The lesser polarity and relatively lower bond energy of P-N bonds compared to P-O bonds make P-N bonds easier to break under the right conditions so that interactions with receptors or targets can be unwound with relative ease. This property makes the interaction with the receptor or target more reversible, thereby increasing its selectivity and activity. Furthermore, the introduction of P-N bonds can change the physicochemical properties of the drug, such as solubility, lipid solubility, etc., thereby improving its absorption and distribution properties. This helps to improve the targeting and tissue selectivity of the drug and reduces unwanted effects on non-targeted tissues.

Fig.1 Prodrug synthesis process involving phosphate group replacement of P-O bond by P-N bond. (Pradere, et al., 2014)

Phosphate Group Replacement of P-O Bond by P-N Bond Service at CD BioGlyco

At CD BioGlyco, our team consists of specialized chemical scientists and engineers with a wealth of experience and in-depth knowledge. Our Glyco™ Synthesis Platform combines advanced synthetic methods and synthesis techniques that can be used to custom synthesize and modify a variety of sugar molecules. Our professional Nucleoside Modification Service and Oligonucleotide Modification Service have received favorable comments from our clients all around the world. We offer a diverse range of phosphate group replacement of P-O bond by P-N bond service, including but not limited to the following:

• We replace the phosphate group with a phosphate ester group by a phosphate esterification reaction and then react compounds containing nucleophilic substituents (such as amines or imines) with the phosphate ester to produce a P-N bond.
• We achieved the P-O to P-N bond transition by using halide and amino substrates reacting successively. First, we use halides (e.g., phosphine chloride, phosphine bromide, etc.) to replace the hydroxyl group in phosphoric acid with a halogen atom to form a phosphate halide. Next, an amino substrate (e.g., hydrogen-ammonia solution, ammonia, etc.) is used to replace the halogen atoms in the phosphate halide with amino groups to form amines of phosphate. This completes the substitution of the P-N bond for the P-O bond.

Fig.2 Flowchart of our services. (CD BioGlyco)

Applications

• Synthesis techniques in which the P-N bond replaces the P-O bond alter the structure and properties of a drug molecule, thereby improving its pharmacological properties, increasing stability, or improving bioavailability.
• The introduction of P-N bond modifying groups with fluorescent dyes into nucleotide molecules enables high sensitivity and high-resolution imaging of DNA or RNA.
• Substitution of P-N bonds for P-O bonds provides new drug design strategies for the research of antitumor, antiviral, and anti-inflammatory drugs.

Advantages of Us

• Our experts will communicate with you to gain a detailed understanding of your needs and objectives to ensure that the approach taken is efficient and sustainable in realizing the replacement of P-O to P-N bonds in phosphates.
• We do our best to help our clients with carbohydrate synthesis and our broad vision will help us to provide high-quality technical service to our clients.
• We have an industry-wide portfolio of scientific products, advanced drug discovery, and manufacturing capabilities.

CD BioGlyco has a proficient team with expertise in chemistry research, development, and innovation. Utilizing advanced technology and knowledge, we offer exceptional phosphate group replacement of P-O bond by P-N Bond service to our clients. If you have any questions about our services or need further information, please feel free to contact our team. We look forward to working with you to provide quality chemical services.