Noncovalent inhibitors of human 20S and 26S proteasome based on trypsin inhibitor SFTI-1.
Sunflower trypsin inhibitor (SFTI-1) is recognized as an attractive scaffold to designed potent inhibitors of various proteases. We have recently found that its analogues inhibit noncovalently both human and yeast 20S proteasomes. Here, a set of novel and more potent in vitro inhibitors is presented. The inhibitory potency of the peptides was assessed with human 20S proteasome in the presence or absence of sodium dodecyl sulfate and with human 26 proteasome. Their antiproliferative action against tumor (human melanoma cells A375) and normal cells (46 BR.1N human fibroblasts and HaCaT keratinocytes) was determined. The selected fluoresceine-labeled inhibitors were able to internalize into A375 cells and were sometimes present as foci in the cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 685-696, 2016.
Department of Biochemistry, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland. dawid.debowski@ug.edu.pl.
Dawid
D
Dębowski
Department of Embryology, Medical University of Gdańsk, Gdańsk, Poland.
Mirosława
M
Cichorek
Department of Biochemistry, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Marta
M
Lubos
Department of Anatomy and Neurobiology, Medical University of Gdańsk, Gdańsk, Poland.
Sławomir
S
Wójcik
Department of Biochemistry, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Anna
A
Łęgowska
Department of Biochemistry, Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Krzysztof
K
Rolka
D045744:Cell Line, Tumor; D006801:Humans; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000737:chemistry / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000494:pharmacology
D010456:Peptides, Cyclic; D061988:Proteasome Inhibitors; C448501:SFTI-1 peptide, sunflower; D014361:Trypsin Inhibitors; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease
SFTI-1 inhibitor; antiproliferative activity; proteasome inhibition