AI Article Synopsis

  • - The study aims to enhance PET imaging tools for detecting bacterial infections by developing a method to incorporate fluorine-18 labeled d-amino acids into bacterial cell structures using a high-throughput chemical biology technique.
  • - A novel radiotracer, [F]FB-sulfo-DBCO, was synthesized and tested, showing significantly higher uptake in bacteria treated with azide-modified d-amino acids compared to control groups.
  • - The findings suggest that the SPAAC-based radiotracer could improve the efficiency of screening d-amino acid-derived PET radiotracers for future imaging applications.

Article Abstract

This study was motivated by the need for better positron emission tomography (PET)-compatible tools to image bacterial infection. Our previous efforts have targeted bacteria-specific metabolism via assimilation of carbon-11 labeled d-amino acids into the bacterial cell wall. Since the chemical determinants of this incorporation are not fully understood, we sought a high-throughput method to label d-amino acid derived structures with fluorine-18. Our strategy employed a chemical biology approach, whereby an azide (-N) bearing d-amino acid is incorporated into peptidoglycan muropeptides, with subsequent "click" cycloaddition with an F-labeled strained cyclooctyne partner. A water-soluble, F-labeled and dibenzocyclooctyne (DBCO)-derived radiotracer ([F]FB-sulfo-DBCO) was synthesized. This tracer was incubated with pathogenic bacteria treated with azide-bearing d-amino acids, and incorporated F was determined via gamma counting. uptake in bacteria previously treated with azide-modified d-amino acids was compared to that in cultures treated with amino acid controls. The biodistribution of [F]FB-sulfo-DBCO was studied in a cohort of healthy mice with implications for future imaging. The new strain-promoted azide-alkyne cycloaddition (SPAAC) radiotracer [F]FB-sulfo-DBCO was synthesized with high radiochemical yield and purity via -succinimidyl 4-[F]fluorobenzoate ([F]SFB). Accumulation of [F]FB-sulfo-DBCO was significantly higher in several bacteria treated with azide-modified d-amino acids than in controls; for example, we observed 7 times greater [F]FB-sulfo-DBCO ligation in cultures incubated with 3-azido-d-alanine versus those incubated with d-alanine. The SPAAC radiotracer [F]FB-sulfo-DBCO was validated via metabolic labeling of azide-bearing peptidoglycan muropeptides. d-Amino acid-derived PET radiotracers may be more efficiently screened via [F]FB-sulfo-DBCO modification.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11036355PMC
http://dx.doi.org/10.1021/acs.bioconjchem.4c00024DOI Listing

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