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Immunization of adult male rabbits with a synthetic luteinizing hormone-receptor peptide (LH-RP; representing amino-acids 21-41 of the extracellular domain of the rat LH receptor) resulted in production of high-titer antibodies capable of interacting with particulate and cell-based LH receptors. The antibody produced was able to inhibit binding of 125I-labeled human chorionic gonadotropin (hCG) to a particulate sheep luteal LH receptor preparation by 40%-50%. Maximal inhibitory activity was correlated with high antibody titer. Immunocytometry revealed that the antibody could directly bind to cells having LH receptors, such as rat granulosa and Leydig cells. The antibodies recognized a 77-kilodalton membrane protein in Western blots of mouse testicular extracts. Interaction of endogenous Leydig cell LH receptor with the LH-RP antibody resulted in both hormone agonist and antagonistic activities. The hormone-mimicking activity (increase in serum testosterone over control) was confined only to the early phase of immunization when the antibody titer was low. Blockade of LH receptor during the later part of immunization resulted in a significant reduction in serum testosterone over controls and inhibition of spermatogenesis. DNA flow cytometry showed that a specific and significant inhibition of meiosis (transformation of primary spermatocytes to round and elongated spermatids P < .01) and spermiogenesis (transformation of round spermatids to elongated spermatids P < .0001) occurred following blockade of LH function.

The delta-toxin is a 26-residue peptide from Staphylococcus aureus with the sequence formyl-MAQDIISTIGDLVKWIIDTVNKFTKK. NMR studies indicate that the segment IISTIGDLVKWIIDTV occurs in an alpha-helical conformation in the toxin. A synthetic peptide corresponding to this segment, although helical, did not exhibit hemolytic activity. Since charged residues like D and K are likely to modulate cytolytic activity, analogs of the 16-residue peptide were synthesized where D was systematically replaced by K. Analogs in which the first D and both Ds were replaced by K showed potent antimicrobial and hemolytic activities. The analog in which the second D was replaced by K was relatively less active. However, all the peptides showed an alpha-helical structure with similar helical content. The activities of the peptides were found to correlate directly with their ability to permeabilize model membranes. Thus, by minimal judicious replacement of charged amino acids, it should be possible to generate cytolytic peptides from short segments of peptide toxins.

The antimicrobial activity of a synthetic peptide corresponding to delta-hemolysin had been examined. The peptide did not exhibit antimicrobial activity against gram negative and gram positive micro-organisms unlike other hemolytic peptides like melittin. This lack of antibacterial activity arises due to the inability of delta-hemolysin to perturb the negatively charged bacterial cell surface and permeabilize the bacterial plasma membrane. However, the red blood cell surface has a structure considerably different from bacteria and does not act as a barrier to molecules reaching the lipid membrane. Hence delta-toxin can lyse erythrocytes. Thus, the specificity in biological activity has been rationalized in terms of differences in the interaction of the toxin with the bacterial and red blood cell surfaces.