التفاصيل البيبلوغرافية
| العنوان: |
Chemoenzymatic syntheses of fluorine-18-labeled disaccharides from [ 18 F]FDG yield potent sensors of living bacteria in vivo . |
| المؤلفون: |
Sorlin AM, López-Álvarez M, Rabbitt SJ, Alanizi AA, Shuere R, Bobba KN, Blecha J, Sakhamuri S, Evans MJ, Bayles KW, Flavell RR, Rosenberg OS, Sriram R, Desmet T, Nidetzky B, Engel J, Ohliger MA, Fraser JS, Wilson DM |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2023 May 20. Date of Electronic Publication: 2023 May 20. |
| نوع المنشور: |
Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Chemoenzymatic techniques have been applied extensively to pharmaceutical development, most effectively when routine synthetic methods fail. The regioselective and stereoselective construction of structurally complex glycans is an elegant application of this approach, that is seldom applied to positron emission tomography (PET) tracers. We sought a method to dimerize 2-deoxy-[ 18 F]-fluoro-D-glucose ([ 18 F]FDG), the most common tracer used in clinical imaging, to form [ 18 F]-labeled disaccharides for detecting microorganisms in vivo based on their bacteria-specific glycan incorporation. When [ 18 F]FDG was reacted with β-D-glucose-1-phosphate in the presence of maltose phosphorylase, both the α-1,4 and α-1,3-linked products 2-deoxy-[ 18 F]-fluoro-maltose ([ 18 F]FDM) and 2-deoxy-2-[ 18 F]-fluoro-sakebiose ([ 18 F]FSK) were obtained. This method was further extended with the use of trehalose (α,α-1,1), laminaribiose (β-1,3), and cellobiose (β-1,4) phosphorylases to synthesize 2-deoxy-2-[ 18 F]fluoro-trehalose ([ 18 F]FDT), 2-deoxy-2-[ 18 F]fluoro-laminaribiose ([ 18 F]FDL), and 2-deoxy-2-[ 18 F]fluoro-cellobiose ([ 18 F]FDC). We subsequently tested [ 18 F]FDM and [ 18 F]FSK in vitro, showing accumulation by several clinically relevant pathogens including Staphylococcus aureus and Acinetobacter baumannii, and demonstrated their specific uptake in vivo. The lead sakebiose-derived tracer [ 18 F]FSK was stable in human serum and showed high uptake in preclinical models of myositis and vertebral discitis-osteomyelitis. Both the synthetic ease, and high sensitivity of [ 18 F]FSK to S. aureus including methicillin-resistant (MRSA) strains strongly justify clinical translation of this tracer to infected patients. Furthermore, this work suggests that chemoenzymatic radiosyntheses of complex [ 18 F]FDG-derived oligomers will afford a wide array of PET radiotracers for infectious and oncologic applications. |
| التعليقات: |
Update in: J Am Chem Soc. 2023 Aug 3;:. (PMID: 37535945) |
| معلومات مُعتمدة: |
R01 EB024014 United States EB NIBIB NIH HHS; R01 EB025985 United States EB NIBIB NIH HHS; R01 EB030897 United States EB NIBIB NIH HHS; R21 AI164684 United States AI NIAID NIH HHS |
| تواريخ الأحداث: |
Date Created: 20230609 Latest Revision: 20231205 |
| رمز التحديث: |
20240628 |
| مُعرف محوري في PubMed: |
PMC10245702 |
| DOI: |
10.1101/2023.05.20.541529 |
| PMID: |
37293043 |
| قاعدة البيانات: |
MEDLINE |
