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.
Lev-Goldman
Vered
V
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Mester
Brenda
B
Ben-Aroya
Nurit
N
Hanoch
Tamar
T
Rupp
Barbara
B
Stanoeva
Tsvetanka
T
Gescheidt
Georg
G
Seger
Rony
R
Koch
Yitzhak
Y
Weiner
Lev
L
Fridkin
Mati
M
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