Host: The 92nd Annual Meeting of the Japanese Pharmacological Society
Name : The 92nd Annual Meeting of the Japanese Pharmacological Society
Number : 92
Location : Osaka
Date : March 14, 2019 - March 16, 2019
Dopamine is the key neuromodulator regulating brain functions and its dysfunctions leading to various neuropsychological disorders such as Parkinson's disease and schizophrenia. Despite much interest, no versatile and safe probe is available that mimic chemical and biological activity of dopamine. Here, we report the development of the first alkyne-tagged neurotransmitter, mono-N-propargylated dopamine (MNPD) as a versatile dopamine prove. MNPD was synthesized from dopamine with five chemical reactions, and is structurally different from endogenous dopamine only by the propargyl group (–CH2 –C≡CH) on its amino group, which suggests minimal effect on the chemical properties. Importantly, the alkynyl group allows coupling of MNPD with azide group (–N3) containing molecules such as fluorophores by Click-Chemistry. Indeed, MNPD was incorporated into dopaminergic neuronal cell lines as well as brain tissues, was fixed at the site, and was able to be visualized by fluorescent microscopy. Furthermore, MNPD showed dopamine-like bioactivity, suggesting MNPD can serve a true biological analog probe of dopamine. In addition to these recent results, other molecule proves, MNPD derivatives, will be discussed.
