Inhibition of cysteine proteases by peptides containing aziridine-2,3-dicarboxylic acid building blocks

Schirmeister, Tanja

doi:10.1002/(sici)1097-0282(1999)51:1<87::aid-bip10>3.0.co;2-z

Cited by 20 publications

(26 citation statements)

References 33 publications

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“…Aziridines are more reactive at low pH [111], with maximum activity at pH 4 due to protonation of the aziridine nitrogen atom, while the epoxides are more reactive at pH 6-7. Another difference between aziridines and epoxides is their hydrogen-bonding abilities [112]. Aziridines are H-bond donors, whereas the epoxides are H-bond acceptors.…”

Section: Peptidyl Aziridines and Epoxidesmentioning

confidence: 99%

Falcipain Inhibition as a Promising Antimalarial Target

Marco¹,

Coteron

2012

CTMC

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Falcipains are Plasmodium falciparum cysteine proteases involved in different processes of the erythrocytic cycle of the malaria parasite like hydrolysis of host hemoglobin, erythrocyte invasion, and erythrocyte rupture. These proteases constitute promising targets in the search for novel therapies that would ease the burden caused by the increasing resistance to current antimalarial drugs. Despite biochemical characterization of four falcipains so far, the search for new falcipain inhibitors has been limited to falcipain-2 and/ or falcipain-3, due to their interesting hemoglobinase capacity and the ample availability of tools to study them. We describe progress towards the discovery of promising falcipain inhibitors, in the light of their drug-like properties and the effect of the inhibition of several of these cysteine proteases. Some important aspects to focus on future development of falcipain inhibition are also discussed.

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Section: Peptidyl Aziridines and Epoxidesmentioning

confidence: 99%

Falcipain Inhibition as a Promising Antimalarial Target

Marco¹,

Coteron

2012

CTMC

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“…mirabilis (20). Derivatives containing aziridine-2-carboxylic acid and aziridine-2,3-dicarboxylic acid as electrophilic building blocks were synthesized to develop new selective inhibitors (25,26). In further investigations, aziridine-based inhibitors containing aziridine-2,3-dicarboxylates [Azi(OBn) 2 s] showed selective inhibition of cathepsin L-like enzymes, for instance, rhodesain, the major trypanosomal papain-like CP of the parasite Trypanosoma brucei rhodesiense (41), and falcipain-2 and falcipain-3 from the malaria parasite Plasmodium falciparum (29).…”

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confidence: 99%

Aziridine-2,3-Dicarboxylate-Based Cysteine Cathepsin Inhibitors Induce Cell Death inLeishmania majorAssociated with Accumulation of Debris in Autophagy-Related Lysosome-Like Vacuoles

Schurigt

Schad

Glowa

et al. 2010

Antimicrob Agents Chemother

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“…It also shows antibacterial activity against Aeromonas salmonesida [59]. Ethyl esters of aziridine-2,3-dicarboxylic acid inhibited the cysteine proteinase papain [60], whereas peptides containing the aziridine-2,3-dicarboxylic acid building block are inhibitors of several cysteine proteases such as the papain-like mammalian proteases [61].…”

Section: Natural Aziridine Alkaloidsmentioning

confidence: 99%