Known ligands

Insulin Analogs. At present, the only known ligands of the insulin receptors are insulin isotypes from different species and a number of synthetic analogs... 

The environment of these systems can be rigidly controlled and systematically varied (eg, ion concentrations). The systems can also be exposed to known ligands if, for example, the liposomes contain specific receptor proteins. 

A comparison of several different steroid receptors with thyroid hormone receptors revealed a remarkable conservation of the amino acid sequence in certain regions, particularly in the DNA-binding domains. This led to the realization that receptors of the steroid or thyroid type are members of a large superfamily of nuclear receptors. Many related members of this family have no known ligand at present and thus are called orphan receptors. The nuclear receptor superfamily plays a critical role in the regulation of gene transcription by hormones, as described in Chapter 43. 

Another group of orphan receptors that as yet have no known ligand bind as homodimers or monomers to direct repeat sequences. 

These teceptors, which may have hormones, metabolites, ot dmgs as ligands, bind to specific DNA elements as homodimers or as heterodimers with RXR. Some—orphan receptors—have no known ligand but bind DNA and influence transcription. 

Phosphine sulfides or selenides are well-known ligands in gold(I) chemistry. With monophosphine complexes of the type [AuX(SPR3)] (X = C1, Br, CN PR3 = PPh3, PCy3, PPh2Py,... 

Scheme 1. A selection of known ligands for homogeneous catalysis...

A pharmacophore hypothesis can be derived from a series of known ligands and their common 3D-features. The pharmacophore is constructed by superimposing energetically favorable conformations of all ligands according to their consensus in structural features. The template structure for the superposition should fulfill two criteria ... 

More recently, in silico target validation has been used. This is similar to the method discussed for ESTs. The DNA sequence of the putative target is compared with those of known liganded receptors. If homologies (similarities) of sequences and structures are determined, they can provide clues to ligands that are likely to interact with the target. 

The use of TADDOL-based ligands offers an important alternative for copper-catalyzed asymmetric 1,4-additions. TADDOLs (a, a, a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol compounds), introduced by Seebach, are among the most successful currently known ligands in asymmetric catalysis. Seebach also developed the first copper-catalyzed 1,4-addition of a Grignard reagent using a TADDOL derivative as a chiral ligand (see Scheme 7.2) [17]. We have reported TADDOL-based... 

The second step comprises similarity searches from known ligands using 2-D descriptors like fingerprints, topological descriptors like atom-pair fingerprints. 

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