title: Synthetic strategies for the biotinylation of bioactive small molecules.
abstract: Biotinylation, the functional appendage of a biotin moiety to a bioactive compound (including small molecules and biological macromolecules), represents a common technique for identification of the intracellular binding partners that underlie the foundation of observed biological activity. Introduction of an attachment tether to the framework of a compound of interest must be planned at an early stage of development, and many considerations apply: 1) region of attachment, so as not to impede the pharmacophore; 2) stability of the parent molecular architecture to biotinylation conditions; 3) regioselectivity for the chosen tethering location over other reactive functionalities; 4) toxicity of reagents if biotinylation is to be performed in vitro; and 5) overall ease of synthesis. This review is intended to serve as a guide for the selection of appropriate tethering modalities. Examples of the common techniques used to affix biotin, including amide bond formation, [3+2] cycloadditions through "click" chemistry, Staudinger ligation, and thioether formation will be discussed, along with analysis of the wider applications of synthetic methodology that have been applied toward the biotinylation of small molecules.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, TX, USA. paul.trippier@ttuhsc.edu
authors.forename: Paul C
authors.initials: PC
authors.lastname: Trippier
mesh_terms: D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000818:Animals; D001710:Biotin / Q000737:chemistry*; D019921:Biotinylation; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D003432:Cross-Linking Reagents / Q000737:chemistry; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D010091:Oximes / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry
chemical_list: D000577:Amides; D000588:Amines; D003432:Cross-Linking Reagents; D006835:Hydrazones; D007097:Imines; D010091:Oximes; D013440:Sulfides; D001710:Biotin