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Affinity Labeling
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
Photoaffinity labeling has emerged as an extremely active area of research. Reagents based on photoactivation have a distinct advantage in that the reactive species, generally a nitrene or carbene, will modify a wide variety of chemical bonds in a protein including insertion into a carbon-carbon bond. Thus, one is not limited by the presence of specific functional groups at the site of interest. In addition, the reactive species can be generated at the site at the convenience of the investigator. The reader is directed to a number of general works on photochemistry78-84 and, in particular to reviews by Bayley and Knowles85 and Bayley86 for a detailed consideration of the chemistry involved in these reactions.
Stimulus-Secretion Coupling: Receptors
Published in Stephen W. Carmichael, Susan L. Stoddard, The Adrenal Medulla 1986 - 1988, 2017
Stephen W. Carmichael, Susan L. Stoddard
High-affinity receptors for atrial natriuretic factor were identified by Rathinavelu and Isom (1988) in PC12 cells. Radioiodinated synthetic atrial natriuretic factor was bound to a single class of high-affinity binding sites that could be characterized. Photoaffinity labeling of the receptor specifically labeled two protein bands. Atrial natriuretic factor receptors on PC12 cells could provide a unique model for the study of this receptor.
Affinity Modification — Organic Chemistry
Published in Dmitri G. Knorre, Valentin V. Vlassov, Affinity Modification of Biopolymers, 1989
Dmitri G. Knorre, Valentin V. Vlassov
Facilitation of the photoaffinity labeling by the target biopolymer according to different mechanism was observed when the same enzyme was subjected to affinity modification with N-nitroso analogues of acetylcholine, methyl(acetoxymethyl)nitrosamine (LXVIII) and methyl(butyroxymethyl)nitrosamine (LXIX).175
Cystic Fibrosis: Proteostatic correctors of CFTR trafficking and alternative therapeutic targets.
Published in Expert Opinion on Therapeutic Targets, 2019
John W. Hanrahan, Yukiko Sato, Graeme W. Carlile, Gregor Jansen, Jason C. Young, David Y. Thomas
Targeting proteostasis and alternative channels holds great promise for CF therapeutics; however, many issues must be addressed. The academic community could develop and employ standard operating procedures for testing CF modulators. Such standards would facilitate the development of therapies. For example, standard methods for assaying correction in cell lines can be useful for primary screens, but validation of compounds in well-differentiated cells is essential to have meaningful estimates of their efficacy and comparisons of correctors. Identifying molecular targets of proteostasis modulators is also a challenge that will be met in the coming years using photoaffinity labeling and mass spectrometry. In the future, proteostasis modulators will be biotinylated and derivatized with benzophenone or phenylazide moieties. After confirming that they can still cause rescue, the derivatized compounds will be used to identify proteostasis targets. Identification of their targets will enable biochemical assays that are often better suited for SAR and lead optimization than cell-based assays and may lead to discovery of entire pathways and alternative targets. All this effort is likely to be worthwhile as the effects of proteostasis modulators and other non-CFTR targets are expected to be additive with those of ‘conventional’ pharmacological chaperones and should benefit patients with CFTR mutations that are not responsive to currently available CFTR modulators. Proteostasis modulators also have a high probability of correcting other mutant proteins and so may be useful for treating other protein trafficking diseases.