Scaffolding ligands scaffolds

The BZ stmcture also has provided a molecular scaffold for a number of peptide receptor ligands (26). Antagonists for the cholecystokinin (CCK-A) receptor, eg, devazepide (65), the thyrotropin-releasing hormone (TRH) receptor, eg, midazolam (66), and the /i -opiate receptor, eg, tifluadom (67), as well as a series of ras famyl transferase inhibitors, eg, BZA-2B (68) (30) have been identified (Table 4). 

The loop region between the two a helices binds the calcium atom. Carboxyl side chains from Asp and Glu, main-chain C =0 and H2O form the ligands to the metal atom (see Figure 2.13b). Thus both the specific main-chain conformation of the loop and specific side chains are required to provide the function of this motif. The helix-loop-helix motif provides a scaffold that holds the calcium ligands in the proper position to bind and release calcium. 

Fluorescently modified fibrils are a useful probe. Furthermore, MacPhee and Dobson have shown that it may be possible to bind other non-peptidic functional groups, provided they can be covalently linked during synthesis. They also demonstrate that utilizing intrinsic fibril structural features might be one approach to the production of peptide scaffolds with well-defined ligand spacings. 

Streptavidin-single-stranded DNA covalent conjugates were described as the building blocks for assembling nanostructured scaffolds [31], The amount and type of biotinylated ligands were used to modulate the affinity of duplex formation between solid-phase-bound nucleic acid templates and DNA-streptavidin conjugates. This system has been proposed for the design of fine-tuned sequence detection systems. 

Mewshaw RE, Edsall RJ, Yang C, Manas ES, Xu ZB, Henderson RA. et al. ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphtha-lene scaffold to achieve ERbeta selectivity. J Med Chem 2005 48 3953-79. 

In addition, Rowlands has involved chiral sulfoxide-containing ligands for the catalytic addition of McsSiCN to aldehydes. " The ligand structure was based on a phenolic oxazoline scaffold with introduction of the sulfur substituent via cysteine derivatives. The best enantioselectivities of up to 61% ee were obtained with the bulkiest tert-butyl substituted ligand (Scheme 10.42). The effect of the sulfoxide configuration was studied, showing that the use of... 

The discovery of the bisphospholane scaffold as a new privileged structure for asymmetric induction in alkene hydroformylation has triggered research for new and improved bisphospholane-type ligands. In this context (k,k)-Ph-bpc has been identified as an excellent ligand for asymmetric hydroformylation, which gives state-of-the-art regio- and enantioselectivities... 

The redox behavior of Nr1 tetraazaannulene complexes can be tuned by the appropriate choice of substituents bound to the ligand scaffold.158 It is interesting to note that in a series of Jager-type Ni11 complexes, both the type (27) and type (28) systems give reversible oxidation, while (29) does not.159... 

Selected further ligand scaffolds that give relatively stable Nini complexes with thioether or thiolate coordination are (78),301 (79),302 and (80).303 The latter can stabilize Ni111 and NiIV, where the Nilv species is prepared by oxidation with HNO3. 

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