A New Bifunctional Chelator Enables Facile Biocoupling and Radiolabeling as the Basis for a Bioconjugation Kit. Issue 7 (10th April 2014)

• Record Type: Journal Article
• Authors: Barandov, Ali; Grünstein, Dan; Apostolova, Ivalaya; Buchert, Ralph; Roger, Michel; Brenner, Winfried; Abram, Ulrich; Seeberger, Peter H.
• Is Part Of: Chembiochem. Volume 15:Issue 7(2014)
• Page Start: 986
• Page End: 994
• Publication Date: 2014-04-10
• Subjects: Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201400001
• Languages: English
• ISSNs: 1439-4227

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A new tridentate bifunctional chelator, <italic>N</italic>‐(‐2‐picolyl)(‐4‐hydroxy)(‐3‐amino)benzoic acid (PHAB), was designed to efficiently coordinate the [^99mTc(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 [^99mTc(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 ^99mTc‐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.</p> </abstract>