Penicilloyl-haptens

G. Christie, N. R. Kitteringham, B. K. Park, Drug-Protein Conjugates - XIII. The Disposition of the Benzyl-Penicilloyl Hapten Conjugated to Albumin , Biochem. Pharmacol. 1987, 36, 3379-3385. 

FIGURE 86-2. Formation of a benzyl penicilloyl hapten-protein complex. 

Czernikov P, Reinharz A, Valloton MB (1974) Immunochemical analysis of rabbit antibodies against vasopressin. Immunochemistry 11 47-53 Dandliker WB, Alonso R, Meyers CY (1967) The synthesis of fluorescent penicilloyl haptens and their use in investigating penicillin antibodies by fluorescence polarization. Immunochemistry 4 295-302... 

Dembo M, Goldstein B, Sobotka AK, Lichtenstein LM (1978) Histamine release due to bivalent penicilloyl haptens Control by the number of cross-linked IgE antibodies on basophil plasma membrane. J Immunol 121 354 De Swarte RD (1972) Drug allergy. In Patterson R (ed) Allergic diseases. Diagnosis and management, Lippincott, Philadelphia... 

With penicillins, opening of the p-lactam bond is possible. The resulting penicilloyl group binds as a hapten to a protein. This may lead to an Ig-E mediated anaphylactic reaction, manifested on the skin as urticaria. 

FIGURE 16.10 Hapten determinants formed by penicillins that contain a p-lactam ring linked to various side chains (R). The primary route of haptenation involves acylation of the E-amino group of lysine residues of serum or cell surface proteins to form a penicilloyl or major antigenic determinant. Isomerization of penicillin leads to the generation of compounds that form disulfide bonds wdth the cysteine sulfhydryl groups of proteins. These epitopes are termed minor determinants. 

Schneider CH, de Week AL (1970) Evaluation of intrinsic and extrinsic penicilloyl-specific immunogenicity of penicillins. The use of penicillin hydrolysis catalyzed by 3,6-bis-(di-methylaminomethyl)catechol. Immunochemistry 7 157-166 Schneider CH, de Week AL, Stauble E (1971 a) Carboxymethyl cellulose additives in penicillins and the elicitation of anaphylactic. Experientia 27 167-168 Schneider CH, Michl J, de Week AL (1971 b) Zur Antigenitat von Hapten-Polysaccharid-Konjugaten. Eur J Immunol 1 98-106... 

Various types of additives introduced in the galenic presentation of drugs such as dyes (e.g., tartrazine) preservatives (e.g., parabens) or filling material (e.g., car-boxymethylcellulose, starch) may function themselves as sensitizers or as inert ma-cromolecular carriers facilitating the formation in vitro of eliciting hapten conjugates. Indeed, it has been shown that carboxymethylcellulose, for example, is an efficient carrier for penicilloyl groups, (Schneider et al. 1971) and may by itself act as sensitizer in cattle (de Weck et al. 1969). 

Otz U, Schneider CH, de Week AL, Gruden E, Gill TG (1978) Induction of immunological tolerance to the penicilloyl antigenic determinant I. Evaluation of BPO-amino acid polymers and copolymers in mice. Eur J Immunol 8 406 Ovary Z, Karush F (1960) Studies on the immunologic mechanism of anaphylaxis I. Anti-body-hapten interactions studied by passive cutaneous anaphylaxis in the guinea pig. J Immunol 84 409... 

Levine BB (1960 c) Formation of D-penicillamine-cysteine mixed disulphide by reaction of D-benzylpenicilloic acide with cysteine Nature 187 940 Levine BB (1961) Studies on the formation of the penicillin antigen. II. Some reactions of D-benzylpenicillenic acid in aqueous solution at pH 7.5. Arch Biochem Biophys 93 50 Levine BB (1962) N(a-D-penicilloyfamines as univalent hapten inhibitors of antibody-de-pendent allergic reactions to penicillin. J Med Chem 5 1025 Levine BB (1963) Studies on the dimensions of the rabbit anti-benzyl penicilloyl antibody combining sites. J Exp Med 117 161... 

Schneider CH, de Week AL (1966b) Chemische Aspekte der Penicillin-AUergie die direkte Bildung der Penicilloyl-Determinanten aus Penicillin. Helv Chim Acta 49 1707 Schneider CH, de Week AL (1967) The reaction of benzylpenicilhn with carbohydrates at neutral pH with a note on the immunogenicity of hapten polysaccharide conjugates. Im-munochemistry 4 331... 

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