title: Hydrogen/deuterium exchange mass spectrometry applied to IL-23 interaction characteristics: potential impact for therapeutics.
abstract: IL-23 is an important therapeutic target for the treatment of inflammatory diseases. Adnectins are targeted protein therapeutics that are derived from domain III of human fibronectin and have a similar protein scaffold to antibodies. Adnectin 2 was found to bind to IL-23 and compete with the IL-23/IL-23R interaction, posing a potential protein therapeutic. Hydrogen/deuterium exchange mass spectrometry and computational methods were applied to probe the binding interactions between IL-23 and Adnectin 2 and to determine the correlation between the two orthogonal methods. This review summarizes the current structural knowledge about IL-23 and focuses on the applicability of hydrogen/deuterium exchange mass spectrometry to investigate the higher order structure of proteins, which plays an important role in the discovery of new and improved biotherapeutics.
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: Roxana E
authors.initials: RE
authors.lastname: Iacob
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Krystek
authors.forename: Richard Y-C
authors.initials: RY
authors.lastname: Huang
authors.forename: Hui
authors.initials: H
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Lin
authors.forename: Paul E
authors.initials: PE
authors.lastname: Morin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Doyle
authors.forename: Adrienne A
authors.initials: AA
authors.lastname: Tymiak
authors.forename: John R
authors.initials: JR
authors.lastname: Engen
authors.forename: Guodong
authors.initials: G
authors.lastname: Chen
mesh_terms: D001691:Biological Therapy; D019295:Computational Biology; D003903:Deuterium / Q000737:chemistry*; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D053759:Interleukin-23 / Q000737:chemistry* / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods; D011485:Protein Binding; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000737:chemistry
chemical_list: C515500:IL23R protein, human; D053759:Interleukin-23; D018123:Receptors, Interleukin; D006859:Hydrogen; D003903:Deuterium
keywords: biotherapeutics; hydrogen/deuterium exchange; interleukins; mass spectrometry; protein binding; protein–protein interactions; structure