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

Abstract

A one-bead one-compound (OBOC) library of peptide-based imaging agents was developed where a 19 F-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 IC 50 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.

Evaluation of Dibenzocyclooctyne and Bicyclononyne Click Reaction on Azido‐Functionalized Antifouling Polymer Brushes via Microspotting

“…[ 11–15 ] Particularly, the strain‐promoted alkyne‐azide cycloaddition (SPAAC) is an outstanding member of this class owing to its excellent chemical stability, non‐toxic and mild reaction conditions, and high coupling efficiency for bio‐orthogonal conjugations. [ 16–19 ]…”

“…[11][12][13][14][15] Particularly, the strain-promoted alkyneazide cycloaddition (SPAAC) is an outstanding member of this class owing to its excellent chemical stability, non-toxic and mild reaction conditions, and high coupling efficiency for bio-orthogonal conjugations. [16][17][18][19] Commonly, azide derivatives are used as bio-tags in biochemistry due to easy integration with biomolecules, for example, in metabolic labeling for living cells with azido functionality, [20,21] post-synthetic modification, [22,23] and in vitro enzymatic transfer. [24,25] Attention has been placed on enhancing the reactivity of cyclooctynes-being the other half in SPAAC-as part of the reactive probes in bio-conjugations.…”

Click Chemistry and Radiochemistry: An Update

“…The straightforward, two-component nature of the SPAAC ligation has made it an attractive tool for radiohalogenation. Indeed, within the past few years, the reaction has been used to label small molecules, ,, biomolecules, and polymers with radiohalogens including fluorine-18, iodine-125, and astatine-211 . In 2018, for example, a group from Bristol-Meyers Squibb modified an anti-PD-L1 protein with a maleimide-bearing variant of azadibenzocyclooctyne (ADIBO) and subsequently reacted the conjugate with an azide-containing, radiofluorinated prosthetic group to create [ 18 F]­F-BMS-986192, an imaging agent capable of delineating PD-L1 expression in a murine model of nonsmall cell lung cancer (Figure A) .…”

Navigating the Expansive Landscapes of Soft Materials: A User Guide for High-Throughput Workflows

“…Immobilized assays are particularly effective in affinity screening, allowing testing against multiple targets and visualization of affinity using dyes or labels. ,,, However, false positives may occur due to autofluorescence or nonspecific interactions between targets or ligands and the solid support. Effective strategies to mitigate these biases include lowering the loading densities, screening replicate libraries, and cross-validating hit materials with solution-phase screening. ,,− Consequently, immobilized screening assays have proven useful in drug discovery and therapeutic development, with emerging potential for incorporation into automated workflows. − …”