Lunedì 22/07 ore 11.30 si terrà il Seminario "Expanding the Repertoire of Nucleosides from GPCRs to Diverse Targets" in aula 0B edificio H3 -

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Data inizio evento: 
22/07/2019 - 11:30
Data fine evento: 
22/07/2019 - 13:00
Data pubblicazione evento
Pubblicato il: 
03/07/2019

SEMINAR NOTICE


Monday, July 22, 2019 at 11:30
Lecture room 0B Building H3, ground floor – Campus P.le Europa

 

Expanding the Repertoire of Nucleosides from GPCRs to Diverse Targets

 

Kenneth A. Jacobson, Ph.D.

 Chief, Molecular Recognition Section, Laboratory of Bioorganic Chemistry

National Institute of Diabetes & Digestive & Kidney Diseases

National Institutes of Health

Bethesda, MD USA

 

 

We study nucleosides and nucleotides at their classical targets in purinergic signaling pathways, e.g. adenosine receptors, P2Y/P2X nucleotide receptors and ribokinases.1 A conformationally constrained, bicyclic ring system (bicyclo[3.1.0]hexane, also called methanocarba) substituted in place of ribose can increase their potency and selectivity at these targets. We have also repurposed this robust scaffold to satisfy the pharmacophoric requirements of various other GPCRs and diverse enzyme and transporter targets. By this approach we discovered novel antagonists of 5HT2 serotonin and k-opioid receptors1,2 and allosteric modulators of the dopamine transporter (DAT).3 This class of rigid nucleosides is indeed a privileged scaffold (but not broadly promiscuous) for the design of novel receptor ligands and potentially as therapeutic agents for a wide variety of conditions.

 

References:

1. Jacobson, et al. Polypharmacology of conformationally locked methanocarba nucleosides. Drug Disc. Today, 2017, 22:1782-1791.

2. Tosh, et al.  Repurposing of a nucleoside scaffold from adenosine receptor agonists to opioid receptor antagonists. ACS Omega, 2018, 3:12658-12678.

3. Tosh, et al.  Scaffold repurposing of nucleosides (adenosine receptor agonists): enhanced activity at the human dopamine and norepinephrine sodium symporters. J. Med. Chem., 2017, 60:3109-3123.

Ultimo aggiornamento: 03-07-2019 - 17:33
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