Molecular Pharmacology, Vol 10, 767-775, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Immunochemical Characterization of a Lysergyl Derivative Incorporated into Protein

¹ Department of Microbiology, University of Illinois, Urbana, Illinois 61801

A derivative of d-lysergic acid diethylamide (LSD), lysergyl_der, previously shown to be covalently coupled to secreted low molecular weight peptides, was shown during incubation in vitro of immune lymphoid cells with LSD to possess structural features closely resembling the parent molecule. Binding studies of LSD and lysergyl_der ligands with antibodies directed against both lysergic acid and lysergyl_der suggested that both antibodies possessed similar specificity. [³H]LSD and [³H]lysergyl_der were bound by anti-lysergyl antibody with average intrinsic association constants (K₀) of 3.5 x 10⁵ M^-1 and 7.8 x 10⁵ M^-1, respectively. Both ligands were bound by anti-lysergyl_der antibody with K₀ values of 1-2 x 10⁵ M^-1. Single-point equilibrium dialysis experiments indicated that both antibody populations bound the derivative in preference to LSD. Mild alkaline hydrolysis of LSD was shown to generate a molecular species which was bound by anti-1ysergyl_der antibody with the same energy as lysergyl_der. Alkaline hydrolysis had no effect on lysergyl_der. These data suggest generation of a demethylated derivative of LSD during incubation of LSD in vitro.