A new bifunctional chelator enables facile biocoupling and radiolabeling as the basis for a bioconjugation kit.
A new tridentate bifunctional chelator, N-(-2-picolyl)(-4-hydroxy)(-3-amino)benzoic acid (PHAB), was designed to efficiently coordinate the [(99m)Tc(CO)3](+) core and facilitate coupling reactions to biomolecules. The chelator can be procured in the form of the corresponding benzotriazole ester (PHAB-OBT), which can be stored and used as a bioconjugation kit. PHAB-OBT reacts with modified carbohydrates with high selectivity and efficiency in a single step in both aqueous and organic media. As is desirable for a kit, no complicated chemical bench work is required. Glycoconjugate postlabeling resulted in neutral radiolabeled glycans with high radiochemical yields. Prelabeling approaches were assessed by successive reaction of PHAB-OBT with the [(99m)Tc(CO)3](+) core and a modified galactose model. The radiolabeled galactose was obtained in 84% yield as defined by HPLC analysis. Biodistribution of the radioactive (99m)Tc-labeled chelator, as well as the glycoconjugates, were examined in mice. Noticeably different biodistribution patterns were observed that reflect trends in the uptake of carbohydrate analogues by various organs.
Max-Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, 14476 Potsdam (Germany); Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 22, 14195 Berlin (Germany).
Ali
A
Barandov
Dan
D
Grünstein
Ivalaya
I
Apostolova
Ralph
R
Buchert
Michel
M
Roger
Winfried
W
Brenner
Ulrich
U
Abram
Peter H
PH
Seeberger
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005690:Galactose / Q000737:chemistry; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008968:Molecular Conformation; D015609:Organotechnetium Compounds / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014230:Triazoles / Q000737:chemistry
D002614:Chelating Agents; D006001:Glycoconjugates; D015609:Organotechnetium Compounds; D012997:Solvents; D014230:Triazoles; C012771:benzotriazole; D005690:Galactose
bioconjugation; carbohydrates; chelator; radiolabeling; technetium-99m