Amino Acid Conjugation

Service Description

Amino acid conjugation is a critical chemical modification technology in drug design and biotech. Altogether amino acids can be paired with small molecules or biomolecules to increase their solubility, bioavailability and targeting. In this way, in addition to maximizing the drug's pharmacological properties, it is more stable in living tissue, less toxic and more effective as a therapeutic agent. BOC Sciences is an acme CRO and bioconjugation industry leader in amino acid conjugating services that help customers increase efficiencies, design drugs more efficiently, and accelerate research at every stage of the development process.

What is Amino Acid Conjugation?

Amino acid conjugating is a process where amino acid molecules are joined to other biomolecules like drugs, peptides, proteins, etc. through chemical reactions. This is typically done to make the target molecule more water-soluble, more distributed in vivo, half-life longer, or more biologically active. Amino acid conjugating reactions generally attach amino or carboxyl groups of amino acids to functional groups of drug molecules by covalent bonding to form stable amino acid conjugates.

Amino acid conjugating is of great importance in drug discovery. There are a lot of drugs or active substances that are poor for absorption, distribution, metabolism and excretion (ADME) in the body because they are highly hydrophobic and weakly water-soluble. Combining amino acids increases the hydrophilicity of these molecules which makes them more soluble and bioavailable making them even more effective.

Fig.1 Advantages of conjugates of amino acids/peptides and bioactive compounds in therapeutic development. (Gattu, Rohith, et al., 2023)

Mechanism of Amino Acid Conjugation

The core mechanism of amino acid conjugation, including phase 2 of metabolism, involves the nucleophilic reaction between the amino group (-NH₂) or carboxyl group (-COOH) in the amino acid and the electrophilic center on the target molecule, resulting in the formation of stable chemical conjugates. During phase 2, the amino acid conjugation is particularly important for enhancing the solubility and facilitating the excretion of xenobiotics and metabolites. These reactions typically involve the interaction of amino acids with small molecule drugs, peptide chains, proteins, or other biomolecules, and are widely used techniques in drug modification and biomolecular engineering. The nucleophilic groups of amino acids, such as amino and carboxyl groups, are able to react efficiently with the electronegative groups in the target molecule, forming various types of chemical bonds. Here are some common conjugating reaction mechanisms.

Amino group and carboxyl group conjugating: The amino group (-NH₂) in amino acids can undergo nucleophilic addition reactions with electrophilic groups such as carboxyl group (-COOH), ester group (-COOR), amide group (-CONH₂) in the target molecule. Through this reaction, a stable chemical conjugating is formed between the amino acid and the target molecule. This type of conjugating is very common in drug design, especially when there is a connection between a small molecule drug and a large biological molecule. For example, in drug synthesis, the combination of amino acids and drug molecules can effectively increase the hydrophilicity of the drug, thereby improving its bioavailability and stability.

Formation of amide bonds: The formation of amide bonds is another reaction that is common in the process of amino acid conjugating. The amino group (-NH₂) in the amino acid can react with the electrophilic functional groups such as the active ester group and the aldehyde group in the target molecule to form an amide bond. Amide bonds are a type of covalent bond with high stability and are suitable for drug modification. In many drug modifications and protein engineering, amide bond formation is used to enhance the stability of the molecular structure. Amide bonds not only improve the biological stability of amino acid conjugates, but also improve the water solubility and in vivo distribution of drugs, prolong the half-life of drugs, and increase targeting.

Formation of dipeptide or tripeptide structure: During the conjugating of amino acids, amino acids can not only conjugate to a single drug molecule, but also react with peptide chains or other amino acid molecules to form a dipeptide (two amino acid residues) or tripeptide (composed of three amino acid residues) structure. This peptide structure is often used to improve the targeting and metabolic stability of drugs. For example, a drug molecule can be combined with specific amino acids to form a specific dipeptide or tripeptide structure, thereby achieving a targeted effect on a specific receptor or cell. In the treatment of tumors or other diseases, the use of peptide chain conjugating technology can increase the selectivity and effectiveness of drugs.

Areas of Application for Amino Acid Conjugation

Amino acid conjugating has a wide range of applications, especially in drug discovery and therapeutics, and has become a common strategy for optimizing drugs. The following are the main application directions of amino acid conjugating:

Improves the water solubility of drugs: Many drugs, especially small molecule drugs, tend to have low water solubility, limiting their absorption and utilization in the body. By combining amino acids with drugs, the hydrophilicity of drugs can be effectively improved, thereby improving their solubility and enhancing bioavailability. For example, drug molecules modified with amino acids can be increased by increasing their absorption when administered orally.

Enhance the targeting of drugs: Through the combination of amino acids, targeted delivery of drugs can be realized. For example, certain amino acids are tissue- or organ-specific, and by conjugating these amino acids, the selectivity of a drug for a specific target can be enhanced. For example, the combination of certain amino acids containing aromatic rings can increase the accumulation of drugs in tumor cells, enabling targeted therapy of tumors.

Extend the half-life of drugs: Many drugs are metabolized quickly in the body, making it difficult to sustain the therapeutic effect of the drug. By conjugating to amino acids, it is possible to reduce the rate at which the drug is metabolized, prolong its half-life in the body, thereby improving its efficacy and reducing the frequency of administration.

Improves drug stability: Amino acid conjugating can also improve the stability of drug molecules, avoiding drug degradation in vivo or during storage. Through the modification of amino acids, the tolerance of drug molecules to environmental factors such as temperature and pH value can be increased, and the expiration date of drugs can be prolonged.

Amino Acid Conjugation Examples

Amino acid conjugating technology has a wide range of applications in drug development, which can significantly improve the performance of drugs, enhance their biological activity and therapeutic effect. Here are some typical examples of amino acid conjugating applications:

Amino acid conjugating to anticancer drugs: In the design of anticancer drugs, amino acid conjugating can significantly improve the accumulation of drugs in tumor cells. Many traditional anti-cancer drugs have the problems of poor targeting and long-lasting efficacy. By introducing amino acid modification into the drug molecule, the drug can conjugate to specific receptors or transporters in tumor cells, thereby improving the targeting of the drug and enhancing the accumulation of the drug in tumor tissue. For example, the use of aromatic amino acids (such as phenylalanine, tyrosine) as drug modification groups can enhance the affinity between the drug and tumor cells, thereby improving the anti-tumor effect. This amino acid-modified anticancer drug is often able to obtain higher concentrations in tumor cells, which increases efficacy and reduces toxicity to normal cells.

Amino acids conjugate to antibiotics: Antibiotics often suffer from poor solubility and low bioavailability, especially for drugs that are poorly water-soluble. By combining with amino acids, the water solubility of the drug can be improved, thereby increasing its bioavailability and absorption. For example, some antibiotics such as penicillin, cephalosporins and other drugs, after being modified with amino acids, can enhance their solubility in the gastrointestinal tract by changing the polarity of the drug, thereby improving the absorption efficiency of the drug. In addition, amino acid modification can also enhance the stability of the drug, extend its half-life in the body, reduce the frequency of dosing, and improve patient compliance.

Amino acid conjugating to vaccines: Amino acid conjugating also has important applications in vaccine development. The immunogenicity of a vaccine often determines its efficacy, and the modification of amino acids can effectively enhance the immunogenicity of antigens. By conjugating amino acids to vaccine antigens, it is possible to increase the stability of antigen molecules, promote their presentation in vivo, and enhance immune responses. For example, the use of certain amino acids (e.g., lysine, glutamic acid, etc.) as part of a vaccine adjuvant can increase the conjugating of antigens to the immune system, making the immune response more pronounced, thereby improving the effectiveness of the vaccine. Such technologies have become important research directions in the development of vaccines against specific pathogens, especially those against tumors or viral diseases.

Our Services

We offer a comprehensive range of amino acid conjugation services, providing customized solutions for various applications in research and drug development. Our services include:

Custom synthesis: We offer tailored amino acid conjugation services, synthesizing conjugates with specific amino acid sequences and functional groups to meet your project requirements.

Amino acid modifications: We provide a variety of modifications, including the conjugation of amino acids with peptides, proteins, fluorescent labels, and other biomolecules for enhanced stability, bioactivity, or targeting.

Peptide conjugation: We specialize in conjugating amino acids to peptides or proteins to improve their stability, solubility, or cellular uptake. This is essential for applications in drug delivery and therapeutic development.

Protein conjugation: Amino acids are conjugated to proteins to modify their activity, targeting capabilities, or pharmacokinetics. We offer customized solutions to meet the needs of various protein engineering projects.

Drug conjugates: We offer the conjugation of amino acids to small molecule drugs, enhancing their bioavailability and specificity for targeted therapy.

Analytical testing and validation: We ensure the integrity and efficacy of amino acid conjugates through a series of tests, including purity analysis, structural verification, and functional assays.

Large-scale production: Equipped to handle large-scale synthesis, we deliver consistent, high-quality amino acid conjugates for industrial and research purposes.

Troubleshooting and optimization: Our team of experts provides troubleshooting and optimization services, addressing challenges in synthesis and improving the overall performance of your conjugates.

Consultation: We offer expert advice on conjugation strategies, project design, and result interpretation, ensuring the success of your research and applications.

With our amino acid conjugation services, you can obtain high-quality conjugates that are vital for advancing your research in drug development, biomaterials, and other specialized applications.

Our Competitive Advantages

Comprehensive Bioconjugation Platform: We offer a proficient and versatile bioconjugation technical platform, providing a wide range of amino acid conjugation services to meet various research and development needs.

Diverse Cross-linking Chemistry: Our services utilize a broad array of cross-linking chemistries, allowing for tailored conjugation strategies that suit different amino acids, peptides, or proteins for optimal results.

Multiple Validation Methods: We employ a variety of techniques to validate protein-peptide binding, ensuring that each amino acid conjugate is accurately synthesized and functional for your specific applications.

High Precision in Conjugation: Our refined conjugation methods ensure precise amino acid binding, enabling you to achieve high-quality conjugates with controlled stoichiometry and minimal byproducts.

Comprehensive Crosslinking Analysis: We provide detailed cross-linking analysis to assess conjugate efficiency and stability, ensuring that you receive reliable data on the performance of your amino acid conjugates.

Detailed Reporting with Results and Discussion: Each project includes a thorough report with comprehensive results, in-depth discussion, and analysis to help you interpret the data and optimize your conjugation strategy.

Quality Services

Peptide Amino Acid Conjugation

Resources

Bioconjugation in Protein Research

Chemical Synthesis of Peptide-Oligonucleotide Conjugates

Bioconjugation in Studying Molecular Interaction

Bioorthogonal Reactions

FAQ

1. Which amino acids are conjugated?

Commonly conjugated amino acids include glycine, glutamine, taurine, ornithine, and serine, which help neutralize and solubilize various metabolites and xenobiotics.

2. What is the role of glycine in amino acid conjugation?

Glycine frequently conjugates with carboxylic acids to form hippuric acid-like derivatives, aiding in the excretion of toxic substances like benzoic acid.

3. What phase of metabolism involves amino acid conjugation?

Amino acid conjugation occurs in phase II metabolism, where it facilitates the excretion of metabolites generated during phase I.

4. How does amino acid conjugation enhance solubility?

By attaching polar amino acids to hydrophobic molecules, conjugation increases their water solubility, enabling efficient elimination from the body.

5. Why is amino acid conjugation important?

It detoxifies potentially harmful compounds, protects cellular integrity, and supports the body's ability to metabolize and excrete drugs and endogenous substances.