Methods for small molecule artificial hapten synthesis: A review from an organic chemist's perspective

The detection of pesticide and veterinary drug residues is crucial for ensuring the safety of food and environmental samples. Small molecule immunoassay technology is extensively used in such analyses due to its high sensitivity and rapid quantification capabilities. The design and synthesis of haptens are key steps in producing high-quality antibodies, as the structure of haptens significantly influences antibody performance. This article reviews the synthesis of small molecule haptens via modification of various functional groups from the perspective of organic synthesis. Organic chemists often lack knowledge of which hapten structures can effectively trigger an immune response, while biologists may not have the knowledge required for the synthesis of haptens. Therefore, collaboration between organic chemists and biologists is highly encouraged. The review also explores different methods for these haptens to react with carrier proteins to form complete antigens. Additionally, the immunogenicity of selected antigens based on synthetic haptens is briefly discussed.