Mild and site-selective 18f-labeling of small molecules and/or biomolecules via a thiol- reactive synthon

Abstract

Site-selective conjugation to biomolecules via thiol-based chemistry is superior to the unselective modification of lysine residues, which produce a mixed product and can potentially interfere with binding affinity of the biomolecule. However, in physiological environments, the maleimide-thiol conjugation product which is the current gold-standard for site-selective thiol-conjugation can be susceptible to hydrolysis or a retro-Michael reaction via exchange with reactive thiols such as those in albumin or glutathione residues yet the degradation is relatively slow. Therefore, for in vivo studies, the maleimide-thiol conjugation proposes instability issues. The compositions and methods disclosed herein provide an alternative thiol-based linkage, one that overcomes the instability issues with conventional reagents and methods. The compositions and methods disclosed herein are useful in various contexts, for example, forF-labeling of peptides/proteins in the preparation of positron emission tomography (PET) probes.