Highlights d Characterization of 33 compounds has identified specific inhibitors of LINE-1s d GBS-149, FTC, and 3TC are non-toxic and mammalianspecific LINE-1 inhibitors d GBS-149 is a new and potent RTi of active human LINE-1s

The mechanism of co-assembly of different aromatic dipeptides has been studied using a combination of microscopy and spectroscopy techniques. At an equimolar ratio, the kinetics of the process is favored giving rise to alternate copolymers.

Primary hyperoxaluria type 1 (PH1) is a rare life-threatening genetic disease related to glyoxylate metabolism and characterized by accumulation of calcium oxalate crystals. Current therapies involve hepatic and/or renal transplantation, procedures that have significant morbidity and mortality and require long-term immunosuppression. Thus, a pharmacological treatment is urgently needed. We introduce here an unprecedented activity of salicylic acid derivatives as agents capable of decreasing oxalate output in hyperoxaluric hepatocytes at the low micromolar range, which means a potential use in the treatment of PH1. Though correlation of this phenotypic activity with glycolate oxidase (GO) inhibition is still to be verified, most of the salicylic acids described here are GO inhibitors with IC values down to 3 μM. Binding mode of salicylic acids inside GO has been studied using in silico methods, and preliminary structure-activity relationships have been established. The drug-like structure and ease of synthesis of our compounds make them promising hits for structural optimization.

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