Immunogenicity studies of a synthetic antigen of alpha methyl dopa.

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Hubbard AK, Lohr CL, Hastings K, Clarke JB, Gandolfi AJ

Immunogenicity studies of a synthetic antigen of alpha methyl dopa.

Immunopharmacol Immunotoxicol. 1993 Nov;15(5):621-37. doi: 10.3109/08923979309019734.

PubMed ID

8301021 [ View in PubMed

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Abstract

Since the idiosyncratic liver toxicity of methyl dopa (L-alpha-methyl-3,4- dihydroxy-phenylalanine) may be due to immune mediated mechanisms, immunologic tools are needed to detect methyl dopa induced antibody and antigen. Hapten (methyl dopa)--carrier (albumin) conjugates were synthesized to generate antibodies reactive with this drug. Studies were also conducted to test the immunogenicity of this hapten-carrier conjugate and its cross reactivity with methyl catechol and levodopa. Methyl dopa (MD), levodopa (LD) or methyl catechol (MC) were conjugated to rabbit serum albumin (RSA) under high pH (base) conditions or by a tyrosinase (tyr) catalyzed reaction. Under the base conjugation conditions, MD-RSA, LD-RSA and MC-RSA conjugates were produced at higher hapten: carrier ratios than conjugates produced by the enzyme catalyzed reaction. Rabbits were subsequently immunized with either MD-RSA(base) or MD-RSA(tyr). Antibodies elicited by MD-RSA(base) had marked reactivity to the carrier protein, albumin, whereas antibodies elicited by MD-RSA(tyr) did not. In addition, reactivity of anti-MD antibody was equal to or greater with MC-RSA than reactivity with either MD-RSA or LD-RSA. This work suggests that the conjugation method using the tyr catalyzed reaction produces the optimal immunogen with minimal modification of the carrier protein. In addition, the catechol moiety of MD, MC and LD appears to be the immunogenic epitope on these haptens.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Methyldopa	Serum albumin	Protein	Humans	No	Binder	Details