Incorporation of Fluorine into an OBOC Peptide Library by Copper-Free Click Chemistry toward the Discovery of PET Imaging Agents

Emily Murrell; Leonard G Luyt

doi:10.1021/acscombsci.9b00146

Incorporation of Fluorine into an OBOC Peptide Library by Copper-Free Click Chemistry toward the Discovery of PET Imaging Agents

ACS Comb Sci. 2020 Mar 9;22(3):109-113. doi: 10.1021/acscombsci.9b00146. Epub 2020 Feb 6.

Authors

Emily Murrell¹, Leonard G Luyt^{1

2

3}

Affiliations

¹ Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada.
² Departments of Oncology and Medical Imaging, University of Western Ontario, 1151 Richmond Street, London, Ontario N6A 5B7, Canada.
³ London Regional Cancer Program, Lawson Health Research Institute, 790 Commissioners Road East, London, Ontario N6A 4L6, Canada.

PMID: 32011850
DOI: 10.1021/acscombsci.9b00146

Abstract

A one-bead one-compound (OBOC) library of peptide-based imaging agents was developed where a ¹⁹F-containing moiety was added onto the N-terminus of octamer peptides through copper-free click chemistry prior to screening of the library. This created a library of complete imaging agents that was screened against CXCR4, a receptor of interest for cancer imaging. The screen directly resulted in the discovery of a peptide-based imaging agent with an IC₅₀ of 138 μM. This proof-of-concept study describes a new type of OBOC peptide library design, where hits discovered from screening can be easily translated into their fluorine-18 counterpart for PET imaging without loss of affinity.

Keywords: CXCR4; OBOC; click chemistry; fluorine-18; molecular imaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Click Chemistry
Combinatorial Chemistry Techniques*
Contrast Media / chemical synthesis*
Contrast Media / chemistry
Drug Discovery*
Fluorine / chemistry*
Molecular Structure
Peptide Library*
Positron-Emission Tomography*

Substances

Contrast Media
Peptide Library
Fluorine