Summavy. The formation of D-penicillamine-L-cystcine mixed disulfide from benzylpenicilloic acid, benzylpenilloic acid and benzylpenicilloyl amide derivatives in 1.-cysteine suspensions a t pH 7,6 and 37" was studied. Thc reaction is faster than direct penicilloylation of proteins known to be a route to penicilloyl antigenic determinants. The production of S-bound penicillamine on protein from penicilloyl compounds must therefore definitely be considered as a potential antigenforming step. The reaction may be partly if not fully blocked by acylation of the thiazolidine nitrogen of penicilloyl compounds. When formylation is applied a considerable rcduction of the capacity of penicilloyl antigenic determinants to interact with anti-penicilloyl antibody is noted. In a number of patients hypersensitive to penicillin, allergic wheal and erythema reactions can be elicited by intracutaneous administration of relatively high doses of sodium benzylpenicilloate. These skin responses do not involve the penicilloyl antigenic determinant because, inter alia, they cannot be correlated with the penicilloyl-specific reactions elicited at the same time by penicilloylated polylysine l) . It has been postulated that D-penicillamine-L-cysteine mixed disulfides may form from penicilloic acid and cysteine residues of host proteins and function as antigenic determinants. According to Leuine [l] , monosodium D-a-benzylpenicilloate reacts in aqueous solution at pH 7.5 with cystine and a product which seems to be D-penicillamine-cysteine mixed disulfide can be separated by paper chromatography. The mechanism could function via an initial disulfide exchange between cystine and penamaldate, present in small amounts in equilibrium with penicilloate. The penamaldic acid-cysteine mixed disulfide thus produced should decompose yielding the observed D-penicillaniine-cysteine mixed disulfide (scheme 1).Our interest in penicillamine determinants is due to the fact, demonstrated in this paper, that in addition to penicilloic acid, functional derivatives of its a-carboxyl group can produce penicillamine-cysteine mixed disulfides in the presence of cystine. Therefore, any penicilloylated carrier within the body has to be regarded as a potential source for the penicillamine determinant. Furthermore, this determinant may arise from low molecular weight penicilloyl derivatives such as e(benzylpenicilloy1)-cr-formyl-L-lysine introduced into the body in large amounts in order to inhibit penicilloyl specific allergic manifestations during penicillin therapy (21. I)The penicilloyl compounds in this paper are functional derivatives of the a-carboxyl group of penicilloic acid. Their isomeric form is ~-a .Acid treated penicilloyl derivatives such as the formvlated ones are isomeric mixtures.

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The synthesis in solution of carboxyl terminal peptide segments of the beta‐subunit of human chorionic gonadotropin is described. The protected segments include sequences 119–131, 132–137, and 138–145. The syntheses were based on a standardized liquid‐liquid extraction program for routine purification of intermediates (two‐phase method). Condensation of terminally deblocked segments afforded protected peptides 132–145, 126–145, 120–145 and 119–145. Protected peptides 126–145 and 120–145 were deprotected in liquid hydrogen fluoride and used in conjugated form for immunization of rabbits. Data on the specificity of the antibody response are reported.