Albert Isidro-Llobet

Sensitized Detection of Inhibitory Fragments and Iterative Development of Non‐Peptidic Protease Inhibitors by Dynamic Ligation Screening

A potential anti‐SARS drug has been developed by dynamic ligation screening (DLS), by which nucleophilic fragments are directed to the proteins active site by reversible reaction with an aldehyde inhibitor. Their inhibitory effect is detected by competition with a fluorogenic enzyme substrate. With this concept, low‐affinity fragments binding specifically to the active site are quickly identified in a functional enzyme assay.WILEY-VCH

EDOTn and MIM, new peptide backbone protecting groups

In recent years, backbone protection has allowed the synthesis of complex peptidic sequences of high interest by preventing chain aggregation and aspartimides formation. Nevertheless, the backbone protectors currently used have some drawbacks: they are difficult to remove and show high steric hindrance. The new backbone protectors presented in this study (EDOTn and MIM) represent an improvement in both aspects.

THAL, a sterically unhindered linker for the solid-phase synthesis of acid-sensitive protected peptide acids.

The 5-(4-hydroxyphenyl)-3,4-ethylenedioxythienyl alcohol (THAL, Thiophene Acid Labile) is described as a new linker for the solid-phase synthesis of peptide carboxylic acids. It is based on the electron-rich 3,4-ethylenedioxythenyl (EDOTn) moiety and allows the obtention of free and tert-butyl-protected peptides by cleavage with 90% and 0.5% TFA, respectively. This very high acid lability makes it useful for the synthesis of sensitive peptides. Free and tert-butyl-protected Leu-enkephalins have been synthesized as models to demonstrate the utility of the linker.