Conjugates of gonadotropin releasing hormone (GnRH) with carminic acid: Synthesis, generation of reactive oxygen species (ROS) and biological evaluation.
We synthesized two carminic acid (7-alpha-d-glucopyranosyl-9,10-dihydro-3,5,6,8-tetrahydroxy-1-methyl-9,10-dioxo-2-anthracene carboxlic acid, CA)-GnRH conjugates to be used as a model for potential photoactive targeted compounds. CA was conjugated to the epsilon-amino group of [d-Lys(6)]GnRH through its carboxylic moiety or via a beta-alanine spacer (beta-ala). Redox potentials of CA and its conjugates were determined. We used electron spin resonance (ESR) and spin trapping techniques to study the light-stimulated redox properties of CA and its CA-GnRH conjugates. Upon irradiation, the compounds stimulated the formation of reactive oxygen species (ROS), that is, singlet oxygen ((1)O(2)) and oxygen radicals (O(2)(-*) and OH(*)). Both conjugates exhibited higher ROS production than the non-conjugated CA. The bioactivity properties of the CA conjugates and the parent peptide, [d-Lys(6)]GnRH, were tested on primary rat pituitary cells. We found that the conjugates preserved the bioactivity of GnRH as illustrated by their capability to induce ERK phosphorylation and LH release.
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Vered
V
Lev-Goldman
Brenda
B
Mester
Nurit
N
Ben-Aroya
Tamar
T
Hanoch
Barbara
B
Rupp
Tsvetanka
T
Stanoeva
Georg
G
Gescheidt
Rony
R
Seger
Yitzhak
Y
Koch
Lev
L
Weiner
Mati
M
Fridkin
D000818:Animals; D002329:Carmine / Q000031:analogs & derivatives* / Q000737:chemistry; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005609:Free Radicals; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry*; D007986:Luteinizing Hormone / Q000378:metabolism; D010084:Oxidation-Reduction; D010766:Phosphorylation; D010777:Photochemistry; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D026082:Singlet Oxygen
D005609:Free Radicals; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D002329:Carmine; D048049:Extracellular Signal-Regulated MAP Kinases