Publications by authors named "Laura Osorio-Planes"

4 Publications

  • Page 1 of 1

A Predictive Approach for the Optical Control of Carbonic Anhydrase II Activity.

ACS Chem Biol 2018 03 9;13(3):793-800. Epub 2018 Feb 9.

Department of Chemistry , Ludwig-Maximilian-University Munich and Munich Center for Integrated Protein Science (CIPSM) , Butenandtstrasse 5-13 , 83177 Munich , Germany.

Optogenetics and photopharmacology are powerful approaches to investigating biochemical systems. While the former is based on genetically encoded photoreceptors that utilize abundant chromophores, the latter relies on synthetic photoswitches that are either freely diffusible or covalently attached to specific bioconjugation sites, which are often native or engineered cysteines. The identification of suitable cysteine sites and appropriate linkers for attachment is generally a lengthy and cumbersome process. Herein, we describe an in silico screening approach that is designed to propose a small number of optimal combinations. By applying this computational approach to human carbonic anhydrase and a set of three photochromic tethered ligands, the number of potential site-ligand combinations was narrowed from over 750 down to 6, which we then evaluated experimentally. Two of these six combinations resulted in light-responsive human Carbonic Anhydrases (LihCAs), which were characterized with enzymatic activity assays, mass spectrometry, and X-ray crystallography. Our study also provides insights into the reactivity of cysteines toward maleimides and the hydrolytic stability of the adducts obtained.
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http://dx.doi.org/10.1021/acschembio.7b00862DOI Listing
March 2018

Photoswitchable thioureas for the external manipulation of catalytic activity.

Org Lett 2014 Mar 10;16(6):1704-7. Epub 2014 Mar 10.

Institute of Chemical Research of Catalonia (ICIQ) , Av. Països Catalans, 16, E-43007 Tarragona, Spain.

A series of azobenzene-based thiourea catalysts have been developed with the aim of achieving control over the catalytic activity by the use of light. The conceptual design of these systems relies on the inactivation by means of intramolecular hydrogen bonding, only likely to take place in one of their isomeric forms. After fine structure modulation of the catalyst a substantial difference in activity has been observed between the irradiated and the nonirradiated reaction. Furthermore, the system allowed in situ manipulation of the catalyst activity during the course of a given experiment.
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http://dx.doi.org/10.1021/ol500381cDOI Listing
March 2014

Enantioselective continuous-flow production of 3-indolylmethanamines mediated by an immobilized phosphoric acid catalyst.

Chemistry 2014 Feb 23;20(8):2367-72. Epub 2014 Jan 23.

Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans, 16, 43007 Tarragona (Spain), Fax: (+34) 977-920-243.

A polystyrene-supported 1,1'-bi-2-naphthol derived phosphoric acid has been synthesized and applied in the enantioselective Friedel-Crafts reaction of indoles and sulfonylimines. The immobilized catalyst was highly active and selective, and gave rise to a broad range of 3-indolylmethanamines (19 examples) in high yields and excellent enantioselectivities (up to 98 % enantiomeric excess) after short reaction times under very convenient reaction conditions (RT in dichloromethane). Moreover, repeated recycling (14 cycles) was possible with no substantial loss in catalytic performance and the system could be adapted to a continuous-flow operation (6 h). Finally, the applicability of the system was further confirmed by rapid access to a library of compounds with three points of diversity in a single continuous-flow experiment that involved sequential pumping of different substrate combinations.
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http://dx.doi.org/10.1002/chem.201303860DOI Listing
February 2014

Polystyrene-supported (2S)-(-)-3-exo-piperazinoisoborneol: an efficient catalyst for the batch and continuous flow production of enantiopure alcohols.

Org Lett 2012 Apr 14;14(7):1816-9. Epub 2012 Mar 14.

Institute of Chemical Research of Catalonia, Av. Països Catalans, 16, E-43007 Tarragona, Spain.

A polystyrene-supported analog (PS-PIB) of 3-exo-morpholinoisoborneol (MIB), designed for increased chemical stability, has been synthesized and used as a ligand in the asymmetric alkylation of aldehydes with Et(2)Zn. The supported ligand turned out to be highly active and enantioselective for a broad scope of substrates (92-99% ee), allowing repeated recycling. A single-pass, continuous flow process implemented with PS-PIB shows only a marginal decrease in conversion after 30 h of operation.
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http://dx.doi.org/10.1021/ol300415fDOI Listing
April 2012