Molecular scaffolds, structure-activity

The synthesis of optically active diaryl methanols 27 is of particular synthetic value, since their core structure represents a molecular scaffold which is relevant to numerous biologically active compounds and pharmaceuticals possessing an-tihistaminic, anticholinergic, local-anesthetic, and laxative properties. Examples include neobenodine 28, orphenadrine 29, and carbinoxamine 30 [31]. 

O. (2004) Synthetic metallonucleases for RNA cleavage. Curr. Opin. Chem. Biol., 8, 192. (e) Molenveld, P., Engbersen, J.F.J. and Reinhoudt, D.N. (2000) Dinuclear metallophosphodiesterase models application of calix[4]arenes as molecular scaffold. Chem. Soc. Rev., 29, 75. (f) Kimura, E. (2000) Dimetallic hydrolases and their models. Curr. Opin. Chem. Biol., 4,207. (g) Williams, N.H., Takasaki, B. and Chin, J. (1999) Structure and nuclease activity of simple dinuclear metal complexes quantitative dissection of the role of metal ions. Acc. Chem. Res., 32, 485. (h) Hegg, E.L. and Burstyn, J.N. (1998) Toward the development of metal-based synthetic nucleases and peptidases a rationale and progress report in applying the principles of coordination chemistry. Coord. Chem. Rev., 173, 133. 

Compared to polymers, dendrimer architectures offer favourable conditions for fixation of catalytically active moieties thanks to their monodispersity, variability, structural regularity of the molecular scaffold, and numerous functionalisation possibilities. Catalytic units can be fixed - multiply if required - on the periphery, in the core of a dendrimer, or at the focal point of a dendron. If the dendrimers are suitably functionalised at the periphery, appropriate metal complexes can be directly attached to the surface of the molecule. In contrast, dendrimers functionalised in the core or at the focal point shield the catalytically active site through their shell structure in a targeted manner, for example to attain substrate selectivity in the case of reactants of different sizes [1]. The corresponding concepts of exodendral and endodendral fixation of catalysts were inttoduced in the context of functionalistion of carbosilane, polyether, and polyester dendrimers [2]. Exodendral fixation refers to attachment of the catalytic units to the... 

Rational inhibitor design offers a compelling alternative for the identification of protein-protein disrupters as it is based on a structural knowledge of the interface. In particular, synthetic scaffolds that mimic the key elements of a protein surface can potentially lead to small molecules with the full activity of a protein domain, a fraction of the molecular weight, and no peptide bonds. Furthermore, lead compounds derived from rational design can be readily optimized by structure-activity relationship (SAR) studies. 

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