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

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages361-371
Number of pages11
JournalAmerican Journal of Reproductive Immunology
Volume48
Issue number6
DOIs
Publication statusPublished - 9 Dec 2002

Fingerprint

Gonadotropin-Releasing Hormone
Fertility
Carrier Proteins
Vaccines
Peptides
Carbodiimides
Tetanus Toxoid
Antibodies
Castration
Gonadotropins
Cysteine
Testosterone

Keywords

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

Cite this

@article{69c498423b724043ac8dacb1295a75ff,
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",
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.",
keywords = "antibodies, anti-fertility, conjugation, C-terminal, GnRH immunoneutralization, N-terminal",
author = "V.A. Ferro and M.A. Khan and E.R. Earl and M.J. Harvey and A. Colston and W.H. Stimson",
year = "2002",
month = "12",
day = "9",
doi = "10.1034/j.1600-0897.2002.01120.x",
language = "English",
volume = "48",
pages = "361--371",
journal = "American Journal of Reproductive Immunology",
issn = "1046-7408",
number = "6",

}

TY - JOUR

T1 - 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

AU - Ferro, V.A.

AU - Khan, M.A.

AU - Earl, E.R.

AU - Harvey, M.J.

AU - Colston, A.

AU - Stimson, W.H.

PY - 2002/12/9

Y1 - 2002/12/9

N2 - 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.

AB - 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.

KW - antibodies

KW - anti-fertility

KW - conjugation

KW - C-terminal

KW - GnRH immunoneutralization

KW - N-terminal

U2 - 10.1034/j.1600-0897.2002.01120.x

DO - 10.1034/j.1600-0897.2002.01120.x

M3 - Article

VL - 48

SP - 361

EP - 371

JO - American Journal of Reproductive Immunology

T2 - American Journal of Reproductive Immunology

JF - American Journal of Reproductive Immunology

SN - 1046-7408

IS - 6

ER -