Synthetic peptide catalysts, development

The points that interest us in the study of cyclic peptides are that the models equipped with several features of biopolymers can be constructed, and that the synthetic cyclic peptides are capable of being biologically active substances. In these respects a further development of the study on cyclic peptides is expected in a future. As is obviously seen in this article, emphasis has been placed on the conformational study of cyclic peptides. The author, who is a polymer organic chemist, hopes that the syntheses of biologically active cyclic peptides and cyclic peptide catalysts will be developed. The point that should be pursued most urgently is the synthesis of cyclic peptides capable of catalyzing asymmetric reactions. 

Cyclo(His-D-Leu) acts as a hydrolytic catalyst. Cyclo(Leu-Gly) blocks the development of (1) physical dependence on morphine, (2) tolerance to the pharmacological effects of /3-endorphin, (3) tolerance to haloperidol-induced catalepsy and hypothermia, and (4) dopaminergic supersensitivity after chronic morphine administration. Cyclo(Tyr-Arg), a synthetic analogue of kyortorphin (an endogenous analgesic peptide), and its A-methyl tyrosine derivatives are more potent than kyotorphin in the mouse tail pressure test. ... 

It must be said that this level of activity is surprising, especially against amide bonds, and intensive efforts to repeat the results are under way. If confirmed this work will be seen as an important advance the design stage may be complex, but with modem synthetic methods peptides of this sort of size are quite reasonable synthetic targets. A practical limitation, as always with enzyme-based mimics, is that - at this stage of development at least - complete success simply means doing a reaction as well as an available natural catalyst. 

Tlie basic study of intermolecular interactions is facihtated by one-bead-one-stRicture libraries which can be powerful tools for the discovery of hgands to synthetic receptors and vice versa. Encoded combinatorial libraries have been useful for disclosing ligands for well-designed macrocyclic host molecules and to elucidate their specificities for peptide sequences. These studies led via receptors with more flexibility to simple host molecules without elaborate design that ai e accessible to combinatorial synthesis. One application is the development of chemical sensors for analytes that are otherwise difficult to detect or only non-specificaUy detected. Such hbraries have been used to find new catalysts and enzyme mimics. 

Enzymatic peptide synthesis, enzyme-catalyzed synthesis, the application of enzymes for peptide bond formation. The very complex ribosomal peptidyl transferase center is not suitable as a catalyst for simple practical peptide synthesis. However, enzymes which usually act as hydrolases, catalyzing the cleavage of peptide bonds, should be considered as peptide ligases due to the principle of microscopic reversibility. The protease-catalyzed peptide synthesis has been developed as a useful tool in the new catalytic synthetic approach based on protease-engineering and the develop-... 

Merrifield peptide synthesis is the most highly developed method of synthesis with solid supports. Every step of the synthesis is carried out in the same polymer. Polymer-supported species also have been used as reagents and catalysts for single step synthetic transformations. Useful single step syntheses should be much easier to achieve than multi-step syntheses in polymer supports because they do not require >99% yield to be valuable. This book emphasizes one step processes in the synthesis of low molecular weight organic compounds carried out with polymer-supported reagents and catalysts. 

Inspired by efficient and stereospecific metal-free enzymatic processes, synthetic chemists have devoted much effort in recent years to the development of a broad spectrum of short peptide-based asymmetric catalysts, which mimic various qualities of enzymes. The structural diversity available with short peptide sequences and the fact that peptides offer to the reactants a more strictly defined asymmetric scaffold, compared to single amino acids, makes this class of molecules particularly promising for the development of a broad spectrum of organic catalysts with fine-tunable structural and electronic properties. 

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