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-α-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 ε-amino group of [d-Lys6]GnRH through its carboxylic moiety or via a β-alanine spacer (β-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 (1O2) and oxygen radicals (O2- 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-Lys6]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.

A natural anthraquinone, carminic acid, was conjugated to GnRH peptide hormone to be used as a model for potential photoactive targeted compounds.Figure optionsDownload as PowerPoint slide