Scaffolding ligands

Solution-Phase Synthesis ofTriazine-Scaffolded Ligands... 

Fig. 10 The use of scaffolding ligands combined with metals to create a 3D cage structure, after Su et al. [54]...

Scheme 4.123 Asymmetric hydroformylation with the assistance of a configurationally stable scaffolding ligand.

Scheme 4.124 Proximal control versus distal control depending on the scaffolding ligand.

SCHEME 14.11. Diastereoselective and enantioselective hydroformylation using a scaffolding ligand. 

SCHEME 14.13. Reaction of 2,5-cyclohexadienyl-l-carbinols via scaffolding ligand-controUed hydroformylation. 

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. 

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