Rational design provides an attractive strategy to tune and control the reactivity of bioinspired catalysts. Although there has been considerable progress in the design of heme oxidase mimetics with active-site environments of ever-growing complexity and catalytic efficiency, their stability during turnover is still an open challenge. Herein, we show that the simple incorporation of two 2-aminoisobutyric acids into an artificial peptide-based peroxidase results in a new catalyst (Fe -MC6*a) with higher resistance against oxidative damage and higher catalytic efficiency. The turnover number of this catalyst is twice as high as that of its predecessor. These results point out the protective role exerted by the peptide matrix and pave the way to the synthesis of robust bioinspired catalysts.

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Inhibition of carbohydrate processing enzymes is a topic of great interest, as these enzymes are involved in a plethora of key biochemical events, such as digestion, lysosomal catabolism of glycoconjugates and post-translational glycoprotein processing. Among the most potent inhibitors of such enzymes, iminosugars have emerged as versatile tools for medicinal chemists, especially those in quest for new therapeutic agents. Supply of iminosugars from natural sources or by chemical synthesis has provided excellent targets for medical intervention, ranging from antidiabetics and antivirals to inhibitors of genetic disorders. Although a huge body of literature has been reported around iminosugars, most data have focused on D-series iminosugars, whereas relatively little attention has been devoted to the corresponding L-enantiomers, due to their supposed lack of biological activity profile, as well as their scarce availability from natural sources. Notwithstanding, recent insights into the molecular details of enzyme-inhibitor interactions have led to a reassessment of L-iminosugars for pharmaceutical purposes. On one hand, they have been used as tools for intensive SAR (structure-activity-relationship) studies, in order to gain new information on the enzymatic inhibition mechanisms. Likewise, early reports on biological activity of L-iminosugars have led to reconsider their therapeutic skills. This review focuses on the most significant discoveries regarding medicinal chemistry of L-iminosugars. The important role L-iminosugars play in unravelling the inhibition mechanisms of specific enzymes is herein recognized; moreover, the high potential of this class of inhibitors as novel drug candidates is under discussion.