Molecular recognition of opioid receptor ligands.
The cloning of the opioid receptors and subsequent use of recombinant DNA technology have led to many new insights into ligand binding. Instead of focusing on the structural features that lead to increased affinity and selectivity, researchers are now able to focus on why these features are important. Site-directed mutagenesis and chimeric data have often been at the forefront in answering these questions. Herein, we survey pharmacophores of several opioid ligands in an effort to understand the structural requirements for ligand binding and selectivity. Models are presented and compared to illustrate key sites of recognition for both opiate and nonopiate ligands. The results indicate that different ligand classes may recognize different sites within the receptor, suggesting that multiple epitopes may exist for ligand binding and selectivity.
University of Minnesota, College of Pharmacy, Department of Medicinal Chemistry, Minneapolis, MN 55455, USA.
Brian E
BE
Kane
Bengt
B
Svensson
David M
DM
Ferguson
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D011957:Receptors, Opioid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D008024:Ligands; D011957:Receptors, Opioid