Heavy Metals Hapten Design and Synthesis

The design, modification, and synthesis of metal-chelate hapten are the first steps to produce antibodies with bound heavy metals hapten that have many potential uses in medicine. As a leading provider in the field of hapten design, Creative Biolabs can accomplish customers' challenging projects for the best-fit design and synthesis of heavy metals hapten.

Contamination of Heavy Metals

During the last decades, heavy metals, such as lead, cadmium, mercury, are the primary toxic contaminants of the continuous risk for human and animal health and may be considered one of the most critical public concerns in food safety and the environment worldwide. Unlike carbon-based contaminants that can be thoroughly degraded, heavy metals are not biodegradable and transform in only a limited number of ways, which lead to the accumulation in the human body with side effects and toxicity for a long time. Exposure of some chemicals containing heavy metals is associated indirectly with autoimmunity as well as immunotoxicity, which may often result in malfunctioning of the immune system, inflammation, sometimes-permanent tissue damage, or even eventually death. Heavy metals are persistent environmental toxins and are implicated in causing carcinogenesis, mutagenesis, and teratogenesis. Due to heavy metal-induced alteration in the immune system and the widespread use of heavy metals in everyday life, the potential for adverse human health effects and environmental pollution has stimulated the increasing concern for the monitor and identification of sites contaminated with heavy metals.

Common structure of the metal-chelate complex. Fig.1 Common structure of the metal-chelate complex.

Metal-chelate Complexes as Haptens

Heavy metals are not immunogen to obtain antibodies because they cannot directly elicit immune responses. However, heavy metals can be added to chelators covalently to be served as metal-chelate complexes and further conjugated to carrier proteins, which are immunogenic and can stimulate an immune response. The antibodies generated may bind to the metal-binding site of the natural molecules or the metal-modified molecules. Previous research results that lead (Pb) loaded with DTPA and covalently coupled to a carrier protein (KLH) produce the complex, and this Pb-chelate hapten is used as an immunogen. It provides evidence that antibody recognition of metal-chelate hapten occurs, and these antibodies exhibit specificity for metal-chelate complexes.

Bifunctional chelators used in the metal-chelate complexes. Fig.2 Bifunctional chelators used in the metal-chelate complexes. (Blake, 2007)

Hapten Design and Synthesis for Heavy Metals

Amongst all the immunoassays development procedures of heavy metal ions, the design and synthesis of the heavy metals hapten are the key steps to the detection of metal ions in environmental and food samples. Based on the suitable bifunctional chelators used to generate the immunogen, hapten design determines the ease of developing antibodies and the specificity of antibodies. In general, the design concept for heavy metals hapten is to generate metal-chelate complexes and metal-chelate-protein conjugates through covalently metal-loaded chelators and subsequently conjugated to carrier proteins. The most frequently used chelators include EDTA and DTPA, cyclohexyl-DTPA, phenanthroline derivative, and carrier proteins contain hemocyanin (KLH), bovine serum albumin (BSA), ovalbumin (OVA), horseradish peroxidase (HRP). The stability constants of metal-chelate interactions guide for the choice of chelators for metal ions. Once the optimal chelator that tightly binds to metals has been chosen, the immunogen can be prepared to synthesize and characterize the conjugate. Based on our advanced hapten design platform and a wealth of knowledge of heavy metals, Creative Biolabs can offer the hapten design and synthesis services for different groups of heavy metals, including but not limited to:

Along with years of extensive experience in offering design and synthesis of haptens, Creative Biolabs could provide the best suitable heavy metals hapten modification and synthesis services to support your projects. We also provide various other hapten design services regarding small molecules. This novel method opens a new way forward for the detection of heavy metals hapten. Please feel free to contact us for more information and a detailed quote.


  1. Blake, D. A.; et al. Antibodies to heavy metals: Isolation, characterization, and incorporation into microplate-based assays and immunosensors. Immunoassay and other Bioanalytical Techniques. 2007: 93-111.
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