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The Multi-Leu peptide inhibitor discriminates between PACE4 and furin and exhibits antiproliferative effects on prostate cancer cells.

Abstract：

:The proprotein convertases (PCs) play an important role in protein precursor activation through processing at paired basic residues. However, significant substrate cleavage redundancy has been reported between PCs. The question remains whether specific PC inhibitors can be designed. This study describes the identification of the sequence LLLLRVKR, named Multi-Leu (ML)-peptide, that displayed a 20-fold selectivity on PACE4 over furin, two enzymes with similar structural characteristics. We have previously demonstrated that PACE4 plays an important role in prostate cancer and could be a druggable target. The present study demonstrates that the ML-peptide significantly reduced the proliferation of DU145 and LNCaP prostate cancer-derived cell lines and induced G0/G1 cell cycle arrest. However, the ML-peptide must enter the cell to inhibit proliferation. It is concluded that peptide-based inhibitors can yield specific PC inhibitors and that the ML-peptide is an important lead compound that could potentially have applications in prostate cancer.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Levesque C,Fugère M,Kwiatkowska A,Couture F,Desjardins R,Routhier S,Moussette P,Prahl A,Lammek B,Appel JR,Houghten RA,D'Anjou F,Dory YL,Neugebauer W,Day R

doi

10.1021/jm3011178

subject

Has Abstract

pub_date

2012-12-13 00:00:00

pages

10501-11

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

55

pub_type

杂志文章

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