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  • Title: Influence of carrier protein conjugation site and terminal modification of a GnRH-I peptide sequence in the development of a highly specific anti-fertility vaccine. Part I.
    Author: Ferro VA, Khan MA, Earl ER, Harvey MJ, Colston A, Stimson WH.
    Journal: Am J Reprod Immunol; 2002 Dec; 48(6):361-71. PubMed ID: 12607772.
    Abstract:
    PROBLEM: We previously immunoneutralized gonadotrophin releasing hormone (GnRH), using an analogue of GnRH (des-1 GnRH-I), conjugated to tetanus toxoid via a carbodiimide reaction. The castration effect on the reproductive system was not consistent in all the treated animals. Therefore, we examined the possibility that conjugation to the carrier protein via the N- or C-terminal could have an effect on efficacy. METHOD OF STUDY: GnRH analogue sequences were synthesized consisting of an additional cysteine at either terminal and specific conjugation was carried out using a bifunctional linker agent. RESULTS: Conjugation of the monomer through the N-terminal proved to be a highly effective means of causing immunocastration in terms of decreased gonadotrophin and testosterone concentrations and testicular size, whereas conjugation through the C-terminal proved to be ineffective. This was reflected in the ability of the antibodies to bind native GnRH, but not the levels of the anti-GnRH antibodies. CONCLUSION: Immunoneutralization efficacy was attributed to the importance of preserving the GnRH C-terminal.
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