Contemporary paradigms for cholinergic ligand design guided by biological structure.
The identification of the various nicotinic receptor subtypes, when coupled with the recent development of three-dimensional structures of surrogate extracellular receptor domains, offers new opportunities to design nicotinic ligands. Conformation and fluctuations in receptor structure are critical to ligand selectivity, and we present here how a flexible receptor template can be used in the development of selective ligands affecting cholinergic neurotransmission.
Taylor
Palmer
P
Department of Pharmacology, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA. pwtaylor@ucsd.edu
Hansen
Scott B
SB
Talley
Todd T
TT
Hibbs
Ryan E
RE
Radić
Zoran
Z
D001665:Binding Sites; D015195:Drug Design; D008024:Ligands; D018722:Nicotinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
D008024:Ligands; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic