Structure-based design, synthesis, and biological evaluation of Leu-Arg dipeptide analogs as novel hepsin inhibitors
- Authors
- Kwon, Hongmok; Kim, YunHye; Park, Kieung; Choi, Soo An; Son, Sang-Hyun; Byun, Youngjoo
- Issue Date
- 15-Jan-2016
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Hepsin; Prostate cancer; Dipeptides; Serine protease
- Citation
- BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, v.26, no.2, pp.310 - 314
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
- Volume
- 26
- Number
- 2
- Start Page
- 310
- End Page
- 314
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/89789
- DOI
- 10.1016/j.bmcl.2015.12.023
- ISSN
- 0960-894X
- Abstract
- Hepsin, a type II transmembrane serine protease, is an attractive protein as a potential therapeutic and diagnostic biomarker for prostate cancer because it is highly up-regulated in prostate cancer and promotes both progression and metastasis. Starting from the reported tetrapeptide hepsin inhibitor Ac-KQLR-ketothiazole (kt) (1), we investigated the minimal structural requirements for hepsin inhibitory activity by truncating amino acids at the N-terminus. The kt and ketobenzothiazole (kbt) dipeptide analogs Ac-LR-kt (3) and Ac-LR-kbt (15) were found to be potent hepsin inhibitors, exhibiting K-i values of 22 nM and 3 nM, respectively. The present work suggests that LR-containing dipeptide molecules could be useful as lead compounds for the development of novel hepsin inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.
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Collections - College of Pharmacy > Department of Pharmaceutical Science > 1. Journal Articles
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