Binding nonpeptide agonists

Nonpeptide Agonists Bind in the Deep Part of the Main Ligand-Binding... 

Not many nonpeptide agonists are yet available, but such compounds have been described — for example, in the angiotensin, CCK, and opioid receptor systems. In fact, for a few receptors, such as the somatostatin, ghrelin, and complement C5A receptors, basically all compounds found by screening using binding assays are agonists. In contrast, for the majority of receptors for which... 

A nonpeptidic agonist ligand of the human C5a receptor synthesis, binding affinity optimization and functional characterization. Bioorg. Med. Chem. Lett. 7 213-218. 

A fourth receptor has been identified and cloned (OP4) based on homology with cDNA sequence of the known (p, 5, and k) opioid receptors (18). Despite the homology in cDNA sequence with known opioid receptors, this new receptor did not bind the classical opioid peptide or nonpeptide agonists... 

Nonpeptide Antagonists May Bind Rather Differently from the Agonist.103... 

Calderon, S.N., Rice, K. C., Rothman, R.B. et al. Probes for narcotic receptor mediated phenomena. 23. Synthesis, opioid receptor binding and bioassay of the highly selective S agonist SNC80 and related novel nonpeptide Sopioid receptor ligands, J. Med. Chem. 1997, 40, 695-704. 

Several nonpeptidic 6-opioid agonists have been synthesized, although none are currently available clinically. These include BW373U86 which is —10 and 20 times more selective for 6-opioid receptor over the p and kappa opioid receptor, respectively, in receptor-binding assays [18]. BW 373U86 also demonstrated high potency (ED50 of 0.2 0.06 nM) in the MVD assay, and its... 

To further address the signaling pathways involved in opioid-induced cardioprotection, Schultz et al. [55] determined the involvement of a Gi/o protein in mediating delta -induced cardioprotection produced by the selective nonpeptide delta opioid agonist, TAN-67. Pretreatment with pertussis toxin for 48 h prior to TAN-67 administration completely blocked its cardioprotective elfect as well as that to IPC, suggesting that a Gi/o protein is intimately involved in the cardioprotection produced by these two interventions. Subsequently, Miki et al. [56] found that morphine produced a cardioprotective elfect in isolated rabbit hearts which was blocked by pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor at a concentration that had no elfect on infarct size in the absence of morphine. More recently, Fryer et al. [57] extended these findings to the intact rat heart and showed that the protective elfect of TAN-67 to reduce infarct size was blocked by chelerythrine and GF 109203X, two selective PKC inhibitors with different binding sites, and that TAN-67 produced a selective translocation of the PKC-delta isoform to the mitochondria. 

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