Design and Synthesis of Haptens for Tetracycline

Combining more than 10 years of experience in the development of small molecule antibodies, Creative Biolabs has specific expertise in designing small molecule/protein carrier adducts. Based on our rich experience in small molecule antigen design and advanced technology platforms, we provide customized services for the design and synthesis of various small molecule haptens, including Tetracycline.

Overview of Tetracycline

Tetracycline, a member of the tetracycline family, is a broad-spectrum naphthacene antibiotic produced semisynthetically from chlortetracycline, an antibiotic isolated from the bacterium Streptomyces aureofaciens. The chemical structure of TC is shown in Fig.1. Its basic chemical structure is mainly a linear fused tetracyclic nucleus (ring marked as A, B, C and D), on which various functional groups are attached. In bacteria, TC binds to the 30S ribosomal subunit and interferes with the binding of aminoacyl-tRNA to the mRNA-ribosomal complex, thereby inhibiting protein synthesis. In addition, it can also bind to the 50S ribosomal subunit of bacteria to a certain extent to change the plasma membrane of the cells, leading to intracellular components to penetrate from bacterial cells. TC is widely used in veterinary medicine, both for therapeutic and preventive purposes, due to its high activity towards a large number of Gram-positive and Gram-negative bacteria.

Chemical structures of tetracycline. Fig.1 Chemical structures of tetracycline. (Wang, 2014)

Synthesis of Haptens for Tetracycline

In previous studies, the conjugation site in TC was usually located in the D ring of TC (Fig.1). In TC, the D and C ring vary, while the A loop is highly conserved. Therefore, in order to generate specific antibodies against TC, the unique moiety of the TC molecule should be exposed to the animal's immune system. Thus, the conjugation site for TC immunogens should be located in the A ring. Pastor-Navarro et al. and Javier Adrian et al have synthesized the haptens of TC, which are characterized by the carboxyl or amino group at the 2 or 4 positions of the A ring, respectively. However, sufficient antibodies cannot be obtained using these haptens.

In order to improve the properties of haptens, Wang et al. synthesized two new haptens of TC (TC-AA and TC-AB) to maximize the exposure of the D and C rings of TC (Fig.2). Hapten TC-AA and TC-AB were prepared through the formation of carboxamido derivatives from the corresponding TC using 4-aminobutyric acid and aminoacetic acid. The haptens retained their tetracyclic nucleus through the aliphatic spacer arm at position 2 of the A ring. Using the activated ester method, these two new haptens are covalently coupled via their carboxyl groups to the lysine amino acid residues of BSA and OVA to form immunogens and coating antigens.

Chemical structures of haptens for tetracycline. Fig.2 Chemical structures of haptens for tetracycline. (Wang, 2014)

Our Service for Haptens Design and Synthesis

Small molecules like antibiotics, although usually capable of interacting with the products of an immune response, often fail to elicit a response on their own. These so-called "haptens" are incomplete antigens. Although they cannot cause immunogenicity or antibody production by themselves, they can be made immunogenic by coupling them with a suitable carrier molecule. Therefore, the preparation of immunogens is a key step in the production of antibodies, especially for small molecule antibodies. Creative Biolabs has many years of experience in small molecule hapten design and synthesis. To make TC immunogenic, our team of experienced experts provides comprehensive TC hapten design and synthesis services, including a selection of carriers, optimization of hapten coupling sites and number, hapten carrier coupling, immunogenicity determination, etc.

Our Advantages

  • Experienced experts and highly skilled technicians
  • First-class technology platform with top equipment
  • Tailored services to meet the specific needs of your scientific research
  • Fast results delivery and competitive prices
  • Perfect pre-sale and after-sales service

In addition to TC, we also provide haptens design and synthesis services for another antibiotic, including aminoglycoside antibiotics, β-lactam antibiotics, macrolide antibiotics, sulfonamide antibiotics, quinolone antibiotics, etc. If you want to know more, please feel free to contact us.

Reference

  1. Wang, Z.; et al. New haptens synthesis, antibody production and comparative molecular field analysis for tetracyclines. RSC Advances. 2014, 4(96): 53788-53794.
All listed services and products are for Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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