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Proteomic effects of budesonide and imiquimod on human bronchial epithelial cells

ABSTRACT: We carry out a comparative proteomic analysis of human bronchial epithelial cells from patients clinically treated or not with inhaled budesonide and stimulated or not with the viral mimic Poly(I:C).We also wanted to investigate the potential anti-viral effects of imiquimod, a TLR7 agonist, on the bronchial epithelial cells proteome in vitro.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung, Epithelial Cell

DISEASE(S): Asthma

SUBMITTER: Juan José Nieto Fontarigo

LAB HEAD: Lena Uller

PROVIDER: PXD029135 | Pride | 2021-11-22

REPOSITORIES: Pride

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			Action	DRS
	2101122_KH_BMC_Sample_29.raw	Raw
	210114_KH_BMC_Sample_1.raw	Raw
	210114_KH_BMC_Sample_14.raw	Raw
	210114_KH_BMC_Sample_15.raw	Raw
	210114_KH_BMC_Sample_16.raw	Raw

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Project description:Chemoselective modification of peptides and proteins has wide applications in chemical biology and pharmaceutical development. A highly efficient chemo-, regio- and stereoselective hydrosulfuration of ynamide was developed by taking advantage of an unprecedented β-addition of the thiols. Importantly, this reaction has been identified as an effective tool for Cys modification of peptides and proteins. The rationally designed strong electron-withdrawing triflyl group on the nitrogen atom of ynamides played a crucial role for controlling the chemo-, regio- and stereoselectivities while another substituent offered a handle for functionality diversification. This Cys modification strategy proceeded efficiently in a slightly basic aqueous conditions (pH 8) to provide exclusively the Z-isomer of the corresponding conjugates with superior stability. All the reactive peptide side chain functional groups such as amino, carboxyl, primary amide, and hydroxyl groups, as well as the unprotected imidazole and indole NH are compatible. This method displayed a broad substrate scope including linear and cyclic peptides, proteins and antibody. The potential application of this method in peptide and protein chemical biology was further exemplified by Cys-bioconjugation with ynamides containing functional molecules including small molecule drugs, fluorescent and affinity tags. In addition, this strategy was also compatible with click chemistry (performed in one-pot), which remarkably extended the application of this tool. Furthermore, the chemoselective biotinylation of ubiquitin(G47C) variant with a biotinylated ynamide, as well as the regioselective modification of Cys14 and Cys38 in bovine pancreatic trypsin inhibitor (BPTI), Cys34 of BSA and the antibody (Trastuzumab), could be accomplished readily under the optimized reaction conditions without perturbation of the other disulfide bonds. This method offered a novel and robust platform for Cys modification and opened new horizons for the production of peptide/protein/antibody-drug conjugates.

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Proteomic effects of budesonide and imiquimod on human bronchial epithelial cells

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