2. Academic Validation
  3. Design and synthesis of dye-conjugated hepsin inhibitors

Design and synthesis of dye-conjugated hepsin inhibitors

  • Bioorg Chem. 2019 Aug:89:102990. doi: 10.1016/j.bioorg.2019.102990.
Kyul Kim 1,  Hongmok Kwon 1,  Doyoung Choi 1,  Taehyeong Lim 1,  Il Minn 2,  Sang-Hyun Son 3,  Youngjoo Byun 4
Affiliations

Affiliations

  • 1 College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Republic of Korea.
  • 2 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, MD 21287, United States.
  • 3 College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Republic of Korea. Electronic address: [email protected].
  • 4 College of Pharmacy, Korea University, 2511 Sejong-ro, Sejong 30019, Republic of Korea. Electronic address: [email protected].
PMID: 31136899 DOI: 10.1016/j.bioorg.2019.102990
Abstract

Hepsin is a type II serine protease that is highly expressed in neoplastic prostate. It is an attractive biomarker for imaging metastatic prostate Cancer because of its overexpression in advanced prostate Cancer and the location of its active site on the cell surface. We designed and synthesized novel hepsin-targeted imaging probes by conjugating the hepsin-binding ligand with near-infrared (NIR) optical dyes. The Leu-Arg dipeptides, attached to BODIPY or SulfoCy7, exhibited strong hepsin-inhibitory activities with Ki values of 21 and 22 nM, respectively. Compound 2 showed selective uptake and retention in hepsin-overexpressing cells. This is the first report of hepsin-targeted optical probes with strong binding affinities and high selectivity over matriptase. Compound 2 has the potential to be used for developing hepsin-based imaging probes and be as a prototype molecule in the design of new hepsin inhibitors.

Keywords

BODIPY; Hepsin; Optical dye; SulfoCy7.

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