Ferro, V.A. and Khan, M.A. and Earl, E.R. and Harvey, M.J. and Colston, A. and Stimson, W.H. (2002) 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. American Journal of Reproductive Immunology, 48 (6). pp. 361-371. ISSN 1600-0897Full text not available in this repository. (Request a copy from the Strathclyde author)
PROBLEM: We previously immunoneutralized gonadotrophin releasing hormone (GnRH), using an analogue of GnRH (des-1 GnRH-1), 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.
|Keywords:||antibodies, anti-fertility, conjugation, C-terminal, GnRH immunoneutralization, N-terminal, Pharmacy and materia medica, Immunology, Obstetrics and Gynaecology|
|Subjects:||Medicine > Pharmacy and materia medica|
|Department:||Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences|
|Depositing user:||Strathprints Administrator|
|Date Deposited:||27 Jul 2011 08:44|
|Last modified:||06 Jan 2017 06:20|