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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(s) -
Ferro Valerie A.,
Khan Mohammad A. H.,
Earl Elizabeth R.,
Harvey Michael J. A.,
Colston Angela,
Stimson William H.
Publication year - 2002
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1034/j.1600-0897.2002.01120.x
Subject(s) - toxoid , peptide , gonadotropin releasing hormone , antibody , chemistry , cysteine , biology , medicine , hormone , endocrinology , biochemistry , immunology , luteinizing hormone , immunization , enzyme
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.