Ligand activated

In addition to halopeiidol, the putative neuroleptics, limcazole (311), lemoxipiide (312), and gevotioline (313) bind to (7-ieceptois as does the dopamine uptake blocker, GBR 12909 (314) and two ligands active at the NMDA receptor, ifenprodil (315) and CNS 1102 (316). NPC 16377, (317) is a selective (7-teceptor ligand. MAO inhibitors and antidepressants also bind to (7-teceptors. Some evidence indicates that (7-teceptors in the brain are in fact a form of cytochrome which may account for the diversity of ligands interacting with (7-sites. 

The ability of receptors to couple to G-proteins and initiate GTPase activity may also be independent of ligand. Thus, specific mutations in a- and P-adrenergic receptors have led to receptors that mediate agonist-independent activation of adenylyl cyclase (69,70). These mutations presumably mimic the conformational state of the ligand-activated receptor when they are activated conventionally by ligands. 

Zirconocene (ligand) Activity (kg PP/g catalyst/h) Weight average molecular weight (kg/mol) Melting point (°C)... 

Kinetic Equations and Ligand Activities under [ligand] > [substrate] 154... 

Table 9 indicates that the rate enhancement (kL/ko) is relatively small when Zn2 + ions or a ligand is used separately for both 50 and 52 substrates. A large rate enhancement is obtained only when a ligand and the metal ion are used together as in the previous examples (Table 1, 3, 4, 7). Ligands L-45 and L-46 are relatively inactive as compared to other ligands having the imidazole moiety. The ligand activation by metal ion is the order of Zn2+ > Co2+ > Ni2+ in all the cases, the same as in non-micellar reactions (Table 1). Rate-enhancing effects (kL/ko) of L-47-Zn2 +, L-48-Zn2 +, and L,L-49-Zn2+ ion complexes are remarkably large in view of the consideration...

The majority of functional assays involve primary signaling. In the case of GPCRs, this involves activation of G-proteins. However, receptors have other behaviors— some of which can be monitored to detect ligand activity. For example, upon stimulation many receptors are desensitized through phosphorylation and subsequently taken into the cell and either recycled back to the cell surface or digested. This process can be monitored by observing ligand-mediated receptor internalization. For... 

G-protein-coupled receptor kinases (GRKs) are a family of enzymes that catalyze the phosphorylation of threonine or serine residues on G-protein-coupled receptors. Characteristically, GRKs only phosphorylate the ligand-activated form of the receptors. Phosphorylation by GRKs usually leads to impaired receptor/G-protein coupling. 

Ligand activation and transformation at heterometallic clusters have been reviewed, but few examples of very mixed -metal clusters effecting these... 

Chalcones Chemical library probed with pharmacophore Ligands active in vitro and in vivo [118]... 

We converted the alkoxyacetyl complexes 9 to the ethyl complex 8, by employing the aforementioned acyl ligand activation and BH reduction procedures, as outlined in Scheme 2. The a, -dialkoxyethylidene salts 9a, b resulted from alkylation of 6a,b with EtsO+PFg" in CH2CI2 recrystallization from CH2CI2-ether provided 9 in 72% yields as air-stable yellow PFg" salts. 

Not surprisingly different ligands activate different members of the STAT family (Table 8.6). Some, such as STATs 1 and 3, are activated by many ligands, whereas others respond to far fewer ligands, e.g. STAT2 appears to be activated only by type I interferons. 

TABLE 20-1 Examples of ligand-activated phosphoinositide hydrolysis in neural tissues... 

Ligand-activated intracellular signaling pathways induce the transcription of ERGs that encode for four categories of cell proteins (1) transcription factors,... 

The mechanisms of corticosteroid receptor regulation of transcription have been elucidated. Both type I and type II corticosteroid receptors are members of a superfamily of ligand-activated transcription factors defined by protein sequence similarity. Included in this superfamily are various other steroid receptors, such as the estrogen receptor, as well as members of the retinoic acid receptor... 

ErbB (or HER in the human). There are four ErbB receptors that form homo- or heterodimers in various combinations upon ligand binding. Specific NRG isoforms preferentially interact with different ErbB dimers. The ErbB receptors are ligand-activated tyrosine kinases structurally similar to the EGF receptor. 

Paech K, Webb P, Kuiper GGJM, Nilsson S, Gustafsson JA, Kushner PJ, et al. (1997) Differential ligand activation of estrogen receptors ERa and ER/S at API sites. Science 77 1508-1510... 

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