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

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• 作者：Olaf Prante ; J&uuml ; rgen Einsiedel ; Roland Haubner ; Peter Gmeiner ; Hans-J&uuml ; rgen Wester ; Torsten Kuwert ; Simone Maschauer
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：January 2007
• 年：2007
• 卷：18
• 期：1
• 页码：254 - 262
• 全文大小：231K
• 年卷期：v.18,no.1(January 2007)
• ISSN：1520-4812

文摘

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 advantageof highly accessible 1,3,4,6-tetra-O-acetyl-2-deoxy-2-[¹⁸F]fluoroglucopyranose, a three-step radiochemical pathwaywas 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 pentapeptideCAKAY, confirming chemoselectivity and excellent conjugation yields of >90% under mild reaction conditions.The optimized method was adopted to the ¹⁸F-glycosylation of the ges/gifchars/alpha.gif" BORDER=0>_vges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₃-affine peptide c(RGDfC), achieving highconjugation yields (95%, decay-corrected). The ges/gifchars/alpha.gif" BORDER=0>_vges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₃ binding affinity of the glycosylated c(RGDfC) remaineduninfluenced as determined by competition binding studies versus ¹²⁵I-echistatin using both isolated ges/gifchars/alpha.gif" BORDER=0>_vges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₃ andhuman umbilical vein endothelial cells (K_i = 68 ± 10 nM (ges/gifchars/alpha.gif" BORDER=0>_vges/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₃) versus K_i = 77 ± 4 nM (HUVEC)). The wholeradiosynthetic procedure, including the preparation of the ¹⁸F-glycosylating reagent Ac₃-[¹⁸F]FGlc-PTS, peptideligation, and final HPLC purification, provided a decay-uncorrected radiochemical yield of 13% after a totalsynthesis time of 130 min. Ac₃-[¹⁸F]FGlc-PTS represents a novel ¹⁸F-labeling reagent for the mild chemoselective¹⁸F-glycosylation of peptides indicating its potential for the design and development of ¹⁸F-labeled bioactiveS-glycopeptides suitable to study their pharmacokinetics in vivo by positron emission tomography (PET).