title: Structural Insight Into Protein Binding of Boron Tracedrug UTX-97 Revealed by the Co-Crystal Structure With Lysozyme at 1.26 Å Resolution.
abstract: Boron neutron capture therapy (BNCT) is one of the numbers of radiotherapies for treatment of certain cancers. The ability of low-dose irradiation with neutrons or radioactive beams to provide an acceptable quality of life is an objective which has not yet been achieved; therefore it will be necessary to increase the efficiency of the neutron capture reaction by lower dose irradiation and by achieving higher drug concentrations in living cells. Drug selectivity in targeting the affected cellular compartment is most important. Molecular design and synthesis of drugs should be based on high resolution structures and analysis of specific compounds and host molecules; however, it is necessary to obtain crystals for X-ray structural analysis. Because compounds containing bulky functional groups are difficult to crystalize due to their flexibility, the method described here makes it possible to stabilize these compounds by complexing them with protein molecules. We have first solved the three-dimensional structure of a BNCT drug-protein molecule combination at 1.26 Å resolution, and discuss the nature of the interaction between a BNCT drug and the protein molecule residues.
authors.affiliation: Research Reactor Institute, Kyoto University, Kumatori, Osaka 590-0494, Japan. Electronic address: morimoto@rri.kyoto-u.ac.jp.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Morimoto
authors.affiliation: Laboratory of Pharmaceutical & Medicinal Chemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Hideko
authors.initials: H
authors.lastname: Nagasawa
authors.affiliation: Institute of Technology and Science, The University of Tokushima, Minamijosanjima, Tokushima 770-8506, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.affiliation: Research Reactor Institute, Kyoto University, Kumatori, Osaka 590-0494, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Chatake
authors.affiliation: Niigata University of Pharmacy and Applied Life Sciences, Akiha-ku, Niigata 956-8603, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hori
mesh_terms: D001665:Binding Sites; D001896:Boron Compounds / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy; D003460:Crystallization; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry*; D011485:Protein Binding; D011810:Quinoxalines / Q000737:chemistry*
chemical_list: D001896:Boron Compounds; D011810:Quinoxalines; C000624960:UTX-97; D009113:Muramidase
keywords: X-ray crystal analysis; boron neutron capture therapy; boron tracedrug; protein structure