title: Creation of a gated antibody as a conditionally functional synthetic protein.
abstract: The ability to conditionally direct antibodies is a potentially powerful application for Synthetic Biology in Medicine. Here we show that control of antibody binding through site-specific, chemical phosphorylation of a recognition domain creates a 'gated' antibody (Ab). This displays a crude Boolean logic where binding is induced in an enzyme-AND-antigen dependent manner. This 'AND-Ab' is therefore active only in the presence of two biomarker inputs: the simultaneous expression of a (cell surface) antigen and secreted enzyme to generate function in vitro, on cells and in mammalian tissue. Such gated Abs, either alone or in combination, could allow the application of logic strategies to enhance precision in biological interrogation, modulation and in therapy.
authors: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
authors: Smita B
authors: SB
authors: Gunnoo
authors: UCB Celltech, 208 Bath Road, Slough, Berkshire SL1 3WE, UK.
authors: Helene M
authors: HM
authors: Finney
authors: UCB Celltech, 208 Bath Road, Slough, Berkshire SL1 3WE, UK.
authors: Terry S
authors: TS
authors: Baker
authors: UCB Celltech, 208 Bath Road, Slough, Berkshire SL1 3WE, UK.
authors: Alastair D
authors: AD
authors: Lawson
authors: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors: Daniel C
authors: DC
authors: Anthony
authors: Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
authors: Benjamin G
authors: BG
authors: Davis
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000378:metabolism*; D000917:Antibody Formation / Q000235:genetics / Q000502:physiology*; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: D000906:Antibodies; D009113:Muramidase