title: Site-Specific In Vivo Bioorthogonal Ligation via Chemical Modulation.
abstract: A critical limitation of bioorthogonal click chemistry for in vivo applications has been its low reaction efficiency due to the pharmacokinetic barriers, such as blood distribution, circulation, and elimination in living organisms. To identify key factors that dominate the efficiency of click chemistry, here a rational design of near-infrared fluorophores containing tetrazine as a click moiety is proposed. Using trans-cyclooctene-modified cells in live mice, it is found that the in vivo click chemistry can be improved by subtle changes in lipophilicity and surface charges of intravenously administered moieties. By controlling pharmacokinetics, biodistribution, and clearance of click moieties, it is proved that the chemical structure dominates the fate of in vivo click ligation.
authors: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA.|Department of Medical Lifescience, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea.
authors: Heebeom
authors: H
authors: Koo
authors: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors: Jeong Heon
authors: JH
authors: Lee
authors: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors: Kai
authors: K
authors: Bao
authors: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA.
authors: Yunshan
authors: Y
authors: Wu
authors: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
authors: Georges
authors: G
authors: El Fakhri
authors: Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA. mhenary1@gsu.edu.
authors: Maged
authors: M
authors: Henary
authors: Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, 65 Landsdowne St., UP-5, Cambridge, MA, 02139, USA. syun@hms.harvard.edu.
authors: Seok Hyun
authors: SH
authors: Yun
authors: Gordon Center for Medical Imaging, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA. hchoi12@mgh.harvard.edu.
authors: Hak Soo
authors: HS
authors: Choi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057930:Click Chemistry / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry*; D008026:Ligation; D051379:Mice; D014018:Tissue Distribution
chemical_list: D005456:Fluorescent Dyes
keywords: click chemistry; near-infrared imaging; pharmacokinetics; real-time imaging; targeted contrast agent