title: Developments of mass spectrometry-based technologies for effective drug development linked with clinical proteomes.
abstract: A strong demand in drug discovery and development today is to overcome "Big Gaps" encountered by differences in species and races, to accelerate effective developments in cost and time, and to meet medical needs. Moreover, drugs of various types have emerged which cover middle-size molecules and polymers rather than conventional small molecules. Upon those challenges, mass spectrometry (MS)-based technologies, which will be described in this paper, will play an increasingly important role, among which the liquid chromatography-tandem mass spectrometry (LC/MS/MS) platform will be powerful as rapid and molecule-based analysis more than ever. nanoPore Optical Interferometry (nPOI) newly introduced can detect even weak interactions in protein-protein and protein-compound, and can be connected directly to LC/MS/MS for identification of binding molecular species, which will be quite useful for affinity ranking and high-throughput interaction screening. Imaging MS provides the molecular information and spatial distribution of targeted molecules within a tissue specimen. MS-based clinical proteomics utilizing clinical specimens and empowered by advanced bioinformatics can attain both key protein-protein interaction (PPI) networks with major protein players responsible for functional mechanisms of a disease subtype. An integration of those MS-based technologies will deliver a seamless platform of drug development from molecules identified in human clinical specimens.
authors.affiliation: Biosys Technologies, Inc., Meguro-ku, Tokyo, Japan. Electronic address: n-nakayama@biosys-tech.co.jp.
authors.forename: Noboru
authors.initials: N
authors.lastname: Nakayama
authors.affiliation: Biosys Technologies, Inc., Meguro-ku, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Bando
authors.affiliation: Biosys Technologies, Inc., Meguro-ku, Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Proteomics Laboratory, Radioisotope Center, The University of Tokyo, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamura
authors.affiliation: Department of Chest Surgery, St. Mariana University School of Medicine, Kanagawa, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Center of Excellence in Biological and Medical Mass Spectrometry, Lund University, BMC, Lund, Sweden.
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
authors.affiliation: Biosys Technologies, Inc., Meguro-ku, Tokyo, Japan; Department of Thoracic and Thyroid Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan; Center of Excellence in Biological and Medical Mass Spectrometry, Lund University, BMC, Lund, Sweden.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nishimura
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D020543:Proteome
keywords: AP-SMALDI; Clinical specimens; H/D exchange; LC-MS/MS/MS; MALDI; MS-based clinical proteomics; Mass spectrometry; Nanopore optical interferometry (nPOI); Protein–protein interaction (PPI); SRM