β-Lactams Hapten Design and Synthesis

Small molecule β-Lactams hapten with good immunogenicity are of great interest for the monoclonal antibodies (mAbs) or polyclonal antibodies (pAbs) preparation. Armed with comprehensive molecular simulation softwares and extensive track record of successful projects in developing small hapten antigen for immunization, Creative Biolabs now provides customized β-Lactams hapten design, modification, and synthesis services for our global clients.

Introduction of β-Lactam Antibiotics

β-Lactam antibiotics are the oldest antimicrobial agents and have the advantages of low toxicity, wide indications, good clinical efficacy, strong anti-bacterial activity in inhibiting the activity of bacterial peptidoglycan transpeptidase and preventing the formation of cell walls. The structure of β-Lactam antibiotics consists of nucleus and side chain. The nucleus contains a four-membered β-Lactam cycle, which fused with the second five- or six-membered ring through N atom and three carbon atoms nearby. According to the differences in parent nuclear structure, β-Lactam antibiotics can be divided into families of penicillins (PENs), cephalosporins (CEPs), monobactams, cephamycins (methoxy cephalosporins, oxacephems), and carbapenems. The β-Lactam ring is a target for nucleophilic attack by free amino groups of proteins, leading to ring-opening and covalent amide bonding of the penicilloyl group. β-Lactam ring is the most unstable part of the chemical structure of β-Lactam antibiotics. Acids, alkalis, some heavy metal ions (oxidant), and exist of alcohols or penicillinase can accelerate the degradation of β-Lactam ring.

Core structure of β-Lactam antibiotics. Fig.1 Core structure of β-Lactam antibiotics.

Hapten Derived from β-Lactam Antibiotics

For the development of a β-Lactam antibiotics-specific immunological assay, mAbs or pAbs against the β-Lactam structure are required. It was reported that scientists once prepared pAbs against ampicillin and established immunoassay techniques for the detection of ampicillin. The cross-reactivity rate between anti-serum and penicillin potassium was 1.5%, and the cross-reactivity rate with oxacillin is 0.4%. None cross-reactivity of streptomycin sulfate, kanamycin, and gentamicin sulfate was found (<0.01%). In another systematic research, ampicillin antigen was coupled with different carrier proteins and the obtained high affinity and high specificity mAbs had nearly no cross-reaction with the carrier proteins and other antibiotics.

What Can Creative Biolabs Do for You?

Creative Biolabs provides Design and Synthesis of Class-specific Haptens for β-Lactams and Design and Synthesis of Compound-specific Haptens for β-Lactams. The essential difference is the structure of the designed haptens. For class-specific haptens, they possess common parent structure. The obtained antibodies raised against parent nucleus can recognize two or more structural analogs at the same time. For compound-specific haptens design, different compounds possess different side-chain structure. The side chain varies from each other and thus became an important marker to distinguish different compounds.

Creative Biolabs also can perform Peptide haptenation by β-Lactams. After adaptation of the solid phase synthesis strategy, β-Lactam peptides are successfully obtained. The specificity and sensitivity of the current analysis approaches have led to the detailed characterization of the modification of peptide by various β-Lactams. The compound 6-aminopenicillanic acid (6-APA) was used as the template to synthesize a series of novel generic haptens that were used to produce the mAbs. The obtained mAbs are broad specific antibodies and capable of recognizing simultaneously up to 11 penicillin drugs. For compound-specific haptens, customized services will be tailored to your needs.

Molecular structures of 6-APA and 11 common penicillin drugs. Fig.2 Molecular structures of 6-APA and 11 common penicillin drugs. (Jiao, 2013)

Hapten Design and Synthesis Services

  • Custom synthesis of reference β-Lactam antibiotics.
  • Custom design and synthesis of specified antibiotics for R&D projects (e.g. from patents or publications).
  • Replacement of labor- and cost-intensive extraction processes by novel synthetic procedures.
  • Upscaling and redesign of syntheses to avoid chromatographic purification.
  • Design, synthesis, and evaluation of β-Lactam antigenic peptide.
  • Haptens design based on 6-APA and other reported or desired template.
  • Factors including the choice of parent nuclear structure and ring structure, the reactive sites, and the desired hapten orientation will be taken into account when designing a β-Lactams hapten.

Having established our unique antigen/immunogen synthesis platforms, especially for smaller antibiotics, Creative Biolabs is capable of meeting quality requirements for customized class-specific or compound-specific β-Lactams antigen design, modification and synthesis. If you are interested in our services, please don’t hesitate to contact us for more information.

Reference

  1. Jiao, S. N.; et al. Synthesis of novel hapten and production of generic monoclonal antibody for immunoassay of penicillins residues in milk. Journal of Environmental Science and Health, Part B. 2013, 48(6): 486-494.
All listed services and products are for Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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