Investigation of structure-activity relationships of synthetic anti-gonadotropin releasing hormone vaccine candidates.
ChemMedChem
; 10(5): 901-10, 2015 May.
Article
en En
| MEDLINE
| ID: mdl-25809441
ABSTRACT
The immunoneutralization of gonadotropin-releasing hormone (GnRH) can be used for the treatment of human hormone-dependent male and female cancers or as immunocontraceptives in animals. Vaccine candidates 1 [Th(K-LP)GnRH], 2 [GnRH(K-LP)Th], 3 [GnRH(K-Th)LP], and 4 [Th(K-GnRH)LP] (for which K=lysine, LP=lipopeptide Ser-Ser-C16 -C16 , and Th=Tâ
helper cell epitope influenza HA2), were synthesized by assembling a CD4(+) Tâ
helper cell epitope (Th), GnRH, and an adjuvanting lipid moiety (LP) in various spatial arrangements. All compounds were efficiently taken up by antigen-presenting cells with significant immunogenicity without an external adjuvant. Compounds 2, 3, and 4, in which GnRH is conjugated through its Câ
terminus, produced higher GnRH-specific antibody responses than construct 1, in which the GnRH moiety is conjugated through its Nâ
terminus. All four constructs induced a significant antiproliferative effect (up to 55 %) on GnRH-receptor-positive LNCaP cells, but showed weaker activity in the GnRH-receptor-negative SKOV-3 cell line. Marked degenerative changes were observed in morphology and follicular development in the ovaries of immunized mice, with approximately 30 % higher degenerative antral and atretic follicles.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vacunas Sintéticas
/
Hormona Liberadora de Gonadotropina
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2015
Tipo del documento:
Article