3,4,6-Tri-O-acetyl-2-deoxy-2-[18F]fluoroglucopyranosyl Phenylthiosulfonate: a Thiol-Reactive Agent for the Chemoselective 18F-Glycosylation of Peptides

Prante O, Einsiedel J, Gmeiner P, Kuwert T (2007)

Publication Type: Journal article

Publication year: 2007

Journal

Bioconjugate Chemistry American Chemical Society

Publisher: American Chemical Society

Book Volume: 18

Pages Range: 254-262

DOI: 10.1021/bc060340v

Abstract

3,4,5-Tri-O-acetyl-2-[¹⁸F]fluoro-2-deoxy-D-glucopyranosyl 1-phenylthiosulfonate (Ac3-[¹⁸F]FGlc-PTS) was developed as a thiol-reactive labeling reagent for the site-specific ¹⁸F- glycosylation of peptides. Taking advantage of highly accessible 1,3,4,6-tetra-O-acetyl-2-deoxy-2-[¹⁸F]fluoroglucopyranose, a three-step radiochemical pathway was investigated and optimized, providing Ac3-[¹⁸F]FGlc-PTS in a radiochemical yield of about 33% in 90 min (decay-corrected and based on starting [¹⁸F]fluoride). Ac3-[¹⁸F]FGlc-PTS was reacted with the model pentapeptide CAKAY, confirming chemoselectivity and excellent conjugation yields of >90% under mild reaction conditions. The optimized method was adopted to the ¹⁸F-glycosylation of the αvβ3-affine peptide c(RGDfC), achieving high conjugation yields (95%, decay-corrected). The αvβ3 binding affinity of the glycosylated c(RGDfC) remained uninfluenced as determined by competition binding studies versus ¹²⁵I-echistatin using both isolated αvβ 3 and human umbilical vein endothelial cells (Ki = 68 ± 10 nM (αvβ3) versus Ki = 77 ± 4 nM (HUVEC)). The whole radiosynthetic procedure, including the preparation of the ¹⁸F-glycosylating reagent Ac3-[ ¹⁸F]FGlc-PTS, peptide ligation, and final HPLC purification, provided a decay-uncorrected radiochemical yield of 13% after a total synthesis time of 130 min. Ac3-[¹⁸F]FGlc-PTS represents a novel ¹⁸F-labeling reagent for the mild chemoselective ¹⁸F- glycosylation of peptides indicating its potential for the design and development of ¹⁸F-labeled bioactive S-glycopeptides suitable to study their pharmacokinetics in vivo by positron emission tomography (PET). © 2007 American Chemical Society.

Authors with CRIS profile

Olaf Prante Professur für Molekulare Bildgebung und Radiochemie Jürgen Einsiedel Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie Torsten Kuwert Lehrstuhl für Klinische Nuklearmedizin

How to cite

APA:

Prante, O., Einsiedel, J., Gmeiner, P., & Kuwert, T. (2007). 3,4,6-Tri-O-acetyl-2-deoxy-2-[18F]fluoroglucopyranosyl Phenylthiosulfonate: a Thiol-Reactive Agent for the Chemoselective 18F-Glycosylation of Peptides. Bioconjugate Chemistry, 18, 254-262. https://doi.org/10.1021/bc060340v

MLA:

Prante, Olaf, et al. "3,4,6-Tri-O-acetyl-2-deoxy-2-[18F]fluoroglucopyranosyl Phenylthiosulfonate: a Thiol-Reactive Agent for the Chemoselective 18F-Glycosylation of Peptides." Bioconjugate Chemistry 18 (2007): 254-262.

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