Thiolactone Peptides as Antibacterial Peptidomimetics

Therapeutic profile In mimicking the quorum-sensing peptides, the thiolactone peptides act as antibacterials, naturally regulating the growth of the bacteria. 

Synthetic highlights This chapter describes the background for the development of modem peptide syntheses. This involves chemical ligation of unprotected peptides carried out with chaotropes. Using a transient thioester-linked intermediate, native chemical ligation (NCL) of two unprotected peptides is achieved. With Fmoc protecting groups and the use of Rink resin, chemoselectivity of peptide synthesis is feasible. The development of NCL, as applied to thiolactone peptide synthesis, is considered in detail. 

This chapter is devoted to a biologically active macrocyclic compound 1, which is neither a dmg molecule that has been introduced into therapy nor was its stereochemistry created by a synthetic chemist. Compound 1 is both a cyclic polypeptide and a macrocyclic thiolactone at the same time. 

The therapeutic importance of peptides and cyclopeptides is well known [1 ]. Their therapeutic profile ranges from anti-diabetic and cytostatic agents in addition 

This compound is a cyclic, non-natural peptide with a thiolactone unit and a representative of the group of cyclic peptide inhibitors of staphylococcal virulence. Thiolactone peptides are expected to act as anti-bacterial therapeutics by a highly specific mechanism, as outlined in the following sections. 

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