TY - JOUR
T1 - 2016 Philip S. Portoghese Medicinal Chemistry Lectureship
T2 - Designing Bivalent or Bitopic Molecules for G-Protein Coupled Receptors. The Whole Is Greater Than the Sum of Its Parts
AU - Newman, Amy Hauck
AU - Battiti, Francisco O.
AU - Bonifazi, Alessandro
N1 - Publisher Copyright:
© This article not subject to U.S. Copyright. Published 2019 by the American Chemical Society.
PY - 2020/3/12
Y1 - 2020/3/12
N2 - The genesis of designing bivalent or bitopic molecules that engender unique pharmacological properties began with Portoghese's work directed toward opioid receptors, in the early 1980s. This strategy has evolved as an attractive way to engineer highly selective compounds for targeted G-protein coupled receptors (GPCRs) with optimized efficacies and/or signaling bias. The emergence of X-ray crystal structures of many GPCRs and the identification of both orthosteric and allosteric binding sites have provided further guidance to ligand drug design that includes a primary pharmacophore (PP), a secondary pharmacophore (SP), and a linker between them. It is critical to note the synergistic relationship among all three of these components as they contribute to the overall interaction of these molecules with their receptor proteins and that strategically designed combinations have and will continue to provide the GPCR molecular tools of the future.
AB - The genesis of designing bivalent or bitopic molecules that engender unique pharmacological properties began with Portoghese's work directed toward opioid receptors, in the early 1980s. This strategy has evolved as an attractive way to engineer highly selective compounds for targeted G-protein coupled receptors (GPCRs) with optimized efficacies and/or signaling bias. The emergence of X-ray crystal structures of many GPCRs and the identification of both orthosteric and allosteric binding sites have provided further guidance to ligand drug design that includes a primary pharmacophore (PP), a secondary pharmacophore (SP), and a linker between them. It is critical to note the synergistic relationship among all three of these components as they contribute to the overall interaction of these molecules with their receptor proteins and that strategically designed combinations have and will continue to provide the GPCR molecular tools of the future.
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U2 - 10.1021/acs.jmedchem.9b01105
DO - 10.1021/acs.jmedchem.9b01105
M3 - Article
C2 - 31499001
AN - SCOPUS:85073122136
SN - 0022-2623
VL - 63
SP - 1779
EP - 1797
JO - Journal of medicinal chemistry
JF - Journal of medicinal chemistry
IS - 5
ER -