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Open AccessArticle

Synthesis of the Novel Covalent Cysteine Proteases Inhibitor with Iodoacetic Functional Group

1
Department of Biochemistry and Neurobiology, Faculty of Materials Science and Ceramics, AGH University of Science and Technology, Mickiewicza 30, 30-059 Krakow, Poland
2
Polish Academy of Sciences, Maj Institute of Pharmacology, Laboratory of Proteomics and Mass Spectrometry, Smetna 12, 31-343 Krakow, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Vincenzo Piccialli
Molecules 2020, 25(4), 813; https://doi.org/10.3390/molecules25040813 (registering DOI)
Received: 14 January 2020 / Revised: 7 February 2020 / Accepted: 12 February 2020 / Published: 13 February 2020
(This article belongs to the Special Issue New Studies on the Synthesis of Biologically Active Products)
This work presents the synthesis of the novel covalent inhibitor of cysteine proteases where epoxide has been replaced by the iodoacetyl functional group. The molecule, similar in action to E-64 and DCG-04, the commonly applied inhibitors, is additionally biotinylated and contains tyrosyl iodination sites. The Fmoc solid phase synthesis has been applied. Conjugation of iodoacetic acid with the peptide was optimized by testing different conjugation agents. The purity of the final product was verified by mass spectrometry and its bioactivity was tested by incubation with a model cysteine protease—staphopain C. Finally, it was shown that the synthesized inhibitor binds to the protein at the ratio of 1:1. More detailed analysis by means of tandem mass spectrometry proved that the inhibitor binds to the cysteine present in the active site of the enzyme. View Full-Text
Keywords: iodoacetic acid; solid phase synthesis; DCG-04; inhibitor; cysteine protease iodoacetic acid; solid phase synthesis; DCG-04; inhibitor; cysteine protease
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MDPI and ACS Style

Hartman, K.; Mielczarek, P.; Silberring, J. Synthesis of the Novel Covalent Cysteine Proteases Inhibitor with Iodoacetic Functional Group. Molecules 2020, 25, 813.

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