Hapten, drug molecule

In order to explain the stimulation of an immune response by small drug molecules, Landsteiner in the 1930 s showed that small molecules could stimulate an immune reaction if combined with a protein. This became the hapten hypothesis, that small molecules could be... 

Hapten A molecule (e.g., a drug metabolite) that becomes attached to an endogenous protein or other tissue macromolecule and so renders it antigenic. 

Homogeneous EIA lend themselves better to dose-response curve linearization than solid-phase EIA. This type of EIA is generally used for the determination of concentrations of small molecules (haptens, drugs). The major supplier of this type of EIA kits (Syva Co.) recommends the plotting of the response variable ( EMIT Units ) vs the log of the concentration or the presentation of the results on special non-linear graph paper provided by them, which is, in fact, logit-log paper. 

The Mannich reaction can be used for the immobilization of certain drugs, steroidal compounds, dyes, or other organic molecules that do not possess the typical nucleophilic groups able to participate in traditional coupling reactions (Hermanson et al., 1992). It also can be used to conjugate hapten molecules to carrier proteins when the hapten contains no convenient nucleophile for conjugation (Chapter 19, Section 6.2). In this case, the carrier protein contains the primary amines and the hapten contains at least one sufficiently active hydrogen to participate in the condensation reaction. 

A rare but serious event that can result from irreversible CYP inhibition is the development of a hypersensitivity reaction. The bioactivation of a drug and the formation of a covalent adduct between the activated substrate and the enzyme can lead to hapten formation and eventually to an idiosyncratic autoimmune response (usually in the form of autoimmune hepatitis) [14]. The hapten formation is the first key step toward the autoimmune response. The CYP macromolecule is made immunogenic ( foreign ) by the covalent binding of the electrophilic metabolites, and the immune reaction follows with the production of autoantibodies against the target molecule (not necessarily alkylated). 

Hapten (Ligand) A small, molecule, such as a drug, that must be coupled to a carrier molecule to induce an... 

The most common of these systems is the enzyme-multiplied immunoassay technique or EMIT, which is particularly suited to the measurement of small molecules (haptens) such as drugs. EMIT is a trade mark of the Syva Corporation of Palo Alto, California. Although it does not involve the separation of bound fraction from free it is nevertheless a competitive assay system. The antigen is labelled with an enzyme in such a way that the enzyme retains its catalytic activity. When the antigen binds to the antibody the enzyme becomes inhibited, probably by an induced conformational change or by steric hindrance of the enzyme active site (Figure 7.15). 

Although molecules with molecular mass greater than 5000 da, such as proteins, glycoproteins, and carbohydrates, can readily elicit a potent antibody formation, molecules such as drugs that have low molecular masses cannot stimulate an immunogenic response. These molecules, widely known as haptens, will bind with preformed antibodies but will not cause antibodies to be produced. 

Radioimmunoassay (RIA) is a very sensitive method used to measure minute quantities of an antigen. Since this method is most often used to measure drugs, toxicants, and other xenobiotics, the antigen used to produce the antibody is the small molecule (hapten) linked covalently to a protein. Among the techniques used in the actual measurement, the antigen capture method, in which the competition between radiolabeled antigen and the unlabeled antigen in the sample, is the most common. 

Halothane (149), first used clinically in the 1950s, is some three times more potent than ether and onset of anesthesia is rapid. Mild, transient hepatotoxicity occurs in about 20% of patients. A much rarer but more severe toxicity has been attributed to a drug-induced hypersensitivity reaction. Under aerobic conditions, halothane is oxidatively metabolized to trifluoroacetyl halide that apparently acylates tissue molecules. The bound trifluoroacetyl moiety functions as a hapten in sensitive individuals triggering the immune response253. 

Hapten A small molecule (e.g., a peptide, hormone, drug, or toxicant) that is conjugated to a larger carrier molecule (a protein) so that an immune response is elicited and antibodies are produced that recognize epitopes on the small molecule. 

---