Strategic synthesis of peptides, labeled peptides and peptidomimetics

Peptides are important class of organic molecules since they are essential for carrying out many biological functions. Recently, there have been increasing efforts to develop methodology for the synthesis of longer peptides and peptide like molecules in solution. The current study describes strategies for the peptide and peptide like molecules synthesis, chemistry of N-subsituted benzotriazoles and importance of peptide and peptidomimetics.;Native chemical ligation (NCL), one of the well-known strategies for the synthesis of peptides and proteins, is a chemoselective and regioselective reaction of peptide thioester and a terminal Cys-peptide that gives a native amide. Based on the native chemical ligation idea, we have developed the formation of native peptides via chemical ligations from tryptophan-containing isopeptides. In this study, we report a statistical, predictive model using an extensive synthetic and computational approach to rationalize the chemical ligation. The feasibility of these traceless chemical ligations is supported by b(N-C) bond distances in N-acyl isopeptides.;Labeled peptides and peptidomimetics have been found to be useful in chemistry, biology, and medicine for monitoring and detection perpose. Usually a chromophoric or fluorophoric unit is attached to a small peptides. Azodyes are a widely used chromophoric units to label peptides. In the current work we have synthesized novel azodye labeled aminoxy acids and peptides which can be used as probes for the same purpose. As an extension to the idea of peptide labeling and potential application of labeled peptidomimetics, we described the synthesis, absorption and fluorescence data of new fluorescent coumarin-labeled depsipeptides. These novel compounds exhibit high emission quantum yields in certain solvents and the emission absorption profiles are highly dependent on the chemical nature (electron donating or withdrawing) of the coumarin unit.;Azapeptides are can mimic natural peptides and can thus imitate or inhibit the same biological effect of a natural peptide. Here we report the development of a phosgene or isocyanate free mild protocol towards the synthesis of azapeptides from amino acid residues using benzotriazole methodology. Stable, crystalline and easy to handle azadipeptidoyl benzotriazoles were prepared and their synthetic utility was demonstrated by the synthesis of longer azapeptides. This novel pathway enabled the solution phase synthesis of an aza-Leuenkephalin analogue. The protocol is revisited in the subsequent chapter which focuses on the de novo design and synthesis of oxyazapeptides in which an amino acid is replaced by an aza-hydroxy acid. Calculations revealed that oxyazapeptides should occupy a beta-turn secondary structure. We also designed and synthesized taurine-containing water-soluble peptidomimetics. N-Terminal and C-terminal taurine acylations allowed the synthesis of a number of taurine-containing peptides, N-, O-taurine conjugates and Sulfonopeptides which can be used for the preparation of bio-active molecules.