Introduction conformationally constrained

The synthesis of conformationally constrained bicyclic and tricyclic compounds, obtained via 5-Exo-Trig iodocyclisation of polybenzylated sugars with an allylic substituent at the anomeric position, is described. The conformation of these molecules has been studied by n.O.e. experiments and Molecular Dynamics calculations. The introduction of an amino and a carboxylic group resulted in the formation of conformationally constrained bicyclic glyco-aminoacids that mimic protein turn conformation. 

The design of new drugs with improved activity is frequently based on the introduction of conformational constraints in order to freeze bioactive conformations of the molecules. For this purpose, a variety of conformationally constrained scaffolds, that can be functionalized with different pharmacophores, have been developed. In this context, carbohydrates appear to be ideal substrates due to their conformational rigidity and offer the possibility of different functionalization of their hydroxyl groups. (/) On the other hand, the introduction of an amino and a carboxylic group into the rigid structure of the carbohydrate, allows to obtain conformationally constrained peptidomimetics,... 

Cross-linking constrains the conformational flexibility of biopolymers and, as a rule, stabilizes their secondary, tertiary, and quaternary structures against the denaturing effects of high temperatures.29 We used differential scanning calorimetry (DSC) to compare the heat-induced conformational transitions of selected RNase A samples that were characterized in Figure 15.2. A brief introduction to DSC is provided in Section 15.15.1 for those readers unfamiliar with this biophysical method. Trace 1 in Figure 15.3a is the heat absorption... 

One strategy to control folding is to direct folds by introduction of S-hairpins, turns which are often associated with Pro incorporation in a polypeptide sequence. Constrained turn mimics have previously been employed in investigations of the active conformation of peptides. Clearly, from the above discussion of CyP and... 

Professor Ubbelohde s suggestions are certainly worthwhile. But there are many directions that we are trying to pursue more detailed studies of the conformation of the polymers, introduction of new functional groups, macro molecular characterization by hydrodynamic methods, and so on. If I were a professor at Imperial College, I could assign all these problems, and those you suggest, to members of the staff but I am constrained by a smaller research group. 

The introduction of conformational restrictions into flexible active molecules is a well-known strategy for trying to increase their potency and/or selectivity toward their biological targets.1 Several methods have been used for constraining flexible molecules. Cyclic derivatives of hnear peptides or peptidomimetics can thus be prepared by reactions involving side-chain... 

A loss in activity after the introduction of a conformational constraint may either be cansed by steric hindrance between the ligand and the receptor, due to the added constraining atoms, or by inability of the ligand to adopt the proper conformation. If activity is retained in the constfained analogue, the analogue is able to adopt the proper conformation, and binding is allowed in spite of the added restricting atoms. 

Cyclization of peptides is an established strategy to stabilize short peptides in an a-helical conformation. Concomitantly, different types of cyclic peptides have been explored as inhibitors of the nuclear receptor-coactivator interaction. Guy et al. have created a library of a-helical constrained peptidomimetics, based on the second nuclear receptor box found in the SRC2 coactivator, by the introduction of a macrolactam bridge [56-58]. The macrolactam bridge induces an a-helical... 

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