Biochemistry

Tutor PharmDr. Helena Mertlíková Kaiserová, Ph.D.
Team Helena Mertlíková Kaiserová
Topic Interactions of nucleoside/nucleotide analogs with cAMP/cGMP-mediated signaling
Faculty FBPT VŠCHT, PřF UK
Abstract

cAMP represents an adenosine triphosphate (ATP) derivative employed by most cells as an intracellular second messenger. It is formed from ATP by the catalytic activity of adenylate cyclases and decomposed by phosphodiesterases to 5’-AMP. Adenylate cyclase pathway generally consists of three structural parts: G-protein, G-protein-coupled receptor (GPCR) and adenylate cyclase itself. GPCR represent an important target for drug development (40-50% of all pharmaceuticals target GPCR). The aim of this work is to study the possibilities of influencing intracellular cAMP (cGMP) levels by the analogs of nucleosides, nucleotides or nucleobases, particularly through the inhibition of adenylate cyclases – either cellular or exogenous (bacterial). This might have implications in the therapy of some infectious and cardiovacular diseases.  Methodological approaches consist of ELISA determination of cyclic nucleotides, HPLC, molecular biology methods and spectral methods. The work requires handling with radioisotopes.