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

V.A. Ferro, M.A. Khan, E.R. Earl, M.J. Harvey, A. Colston, W.H. Stimson

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15 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)361-371
Number of pages11
JournalAmerican Journal of Reproductive Immunology
Volume48
Issue number6
DOIs
Publication statusPublished - 9 Dec 2002

Keywords

  • antibodies
  • anti-fertility
  • conjugation
  • C-terminal
  • GnRH immunoneutralization
  • N-terminal

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