Ribosomally expressed proteins perform multiple, versatile, and specialized tasks throughout Nature. In modern times, chemically modified proteins, including improved hormones, enzymes, and antibody-drug-conjugates have become available and have found advanced...

Cyclic peptides are promising next‐generation therapeutics with improved biological stability and activity. A catalyst‐free stapling method for cysteine‐containing peptides has been developed that enables fine‐tuning of the macrocycle by using the appropriate regioisomers of fluorobenzene linkers. Stapling was performed on the unprotected linear peptide or, more conveniently, directly on‐resin after peptide synthesis. NMR spectroscopy and circular dichroism studies demonstrate that the type of stapling can tune the secondary structures of the peptides. The method was applied to a set of potential agonists for melanocortin receptors, generating a library of macrocyclic potent ligands with ortho, meta or para relationships between the thioethers. Their small but significant differences in potency and efficacy demonstrate how the method allows facile fine‐tuning of macrocyclic peptides towards biological targets from the same linear precursor.

Sulphur-selective conjugate addition reactions play a central role in synthetic chemistry and chemical biology. A general tool for conjugate addition reactions should provide high selectivity in the presence of competing...

New solid-phase based methods have allowed efficient synthesis of natural products and novel peptide hormone derivatives with a C-terminal lactam.