Molecules, Vol. 25, Pages 4904: Computational Studies towards the Identification of Novel Rhodopsin-Binding Compounds as Chemical Chaperones for Misfolded Opsins
Molecules, Vol. 25, Pages 4904: Computational Studies towards the Identification of Novel Rhodopsin-Binding Compounds as Chemical Chaperones for Misfolded Opsins
Molecules doi: 10.3390/molecules25214904
Authors:
Gaia Pasqualetto
Martin Schepelmann
Carmine Varricchio
Elisa Pileggi
Caroline Khogali
Siân R. Morgan
Ian Boostrom
Malgorzata Rozanowska
Andrea Brancale
Salvatore Ferla
Marcella Bassetto
Accumulation of misfolded and mistrafficked rhodopsin on the endoplasmic reticulum of photoreceptor cells has a pivotal role in the pathogenesis of retinitis pigmentosa and a subset of Leber’s congenital amaurosis. One potential strategy to reduce rhodopsin misfolding and aggregation in these conditions is to use opsin-binding compounds as chemical chaperones for opsin. Such molecules have previously shown the ability to aid rhodopsin folding and proper trafficking to the outer cell membranes of photoreceptors. As means to identify novel chemical chaperones for rhodopsin, a structure-based virtual screening of commercially available drug-like compounds (300,000) was performed on the main binding site of the visual pigment chromophore, the 11-cis-retinal. The best 24 virtual hits were examined for their ability to compete for the chromophore-binding site of opsin. Among these, four small molecules demonstrated the ability to reduce the rate constant for the formation of the 9-cis-retinal-rhodopsin complex, while five molecules surprisingly enha...
Source: Molecules - Category: Chemistry Authors: Gaia Pasqualetto Martin Schepelmann Carmine Varricchio Elisa Pileggi Caroline Khogali Si ân R. Morgan Ian Boostrom Malgorzata Rozanowska Andrea Brancale Salvatore Ferla Marcella Bassetto Tags: Article Source Type: research