title: Photoregulation of α-Chymotrypsin Activity by Spiropyran-Based Inhibitors in Solution and Attached to an Optical Fiber.
abstract: Here the synthesis and characterization of a new class of spiropyran-based protease inhibitor is reported that can be reversibly photoswitched between an active spiropyran (SP) isomer and a less active merocyanine (MC) isomer upon irradiation with UV and visible light, respectively, both in solution and on a surface of a microstructured optical fiber (MOF). The most potent inhibitor in the series (SP-3 b) has a C-terminal phenylalanyl-based α-ketoester group and inhibits α-chymotrypsin with a Ki of 115 nM. An analogue containing a C-terminal Weinreb amide (SP-2 d) demonstrated excellent stability and photoswitching in solution and was attached to the surface of a MOF. The SP isomer of Weinreb amide 2 d is a competitive reversible inhibitor in solution and also on fiber, while the corresponding MC isomer was significantly less active in both media. The ability of this new class of spiropyran-based protease inhibitor to modulate enzyme activity on a MOF paves the way for sensing applications.
authors.affiliation: ARC Centre of Excellence for Nanoscale BioPhotonics, Institute for Photonics and Advanced Sensing and Department of Chemistry, The University of Adelaide, South Australia, 5005 (Australia).
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Zhang
authors.affiliation: ARC Centre of Excellence for Nanoscale BioPhotonics, Institute for Photonics and Advanced Sensing and Department of Chemistry, The University of Adelaide, South Australia, 5005 (Australia).
authors.forename: Sabrina
authors.initials: S
authors.lastname: Heng
authors.affiliation: ARC Centre of Excellence for Nanoscale BioPhotonics, Institute for Photonics and Advanced Sensing and Department of Chemistry, The University of Adelaide, South Australia, 5005 (Australia). andrew.abell@adelaide.edu.au.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Abell
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D007536:Isomerism; D008027:Light; D062105:Molecular Docking Simulation; D009574:Nitro Compounds / Q000737:chemistry* / Q000494:pharmacology; D055100:Optical Fibers; D055668:Photochemical Processes; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D001578:Benzopyrans; D007211:Indoles; D009574:Nitro Compounds; D011480:Protease Inhibitors; C548873:merocyanine; C088184:spiropyran; D002918:Chymotrypsin; C117608:alpha-chymotrypsin
keywords: enzymes; peptidomimetics; photoswitching; spiropyran; surface chemistry