| Selectivity of labeled bromoethylamine for protein alkylation. | |
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MedLine Citation:
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PMID: 22643979 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alkylation of cysteine residues has been used extensively for characterization of proteins and their mode of action in biological systems, research endeavors that are at the core of proteomics. Treatment with a simple alkylating agent such as [2-(13)C] bromoethylamine would result in labeled thialysine at the ε-position. This chemical modification of proteins would allow investigations via both (13)C NMR spectroscopy and mass spectrometry. However [2-(13)C] labeled bromoethylamine is not available commercially. We investigated its synthesis at acid pH with the goal of obtaining singly labeled bromoethylamine and understanding the mechanistic details of the reaction. Based on our experimental and theoretical results, bromination of [2-(13)C] labeled ethanolamine in acidic conditions takes place via exclusive attack of the nucleophile (HBr) at the hydroxyl bearing C. Moreover, hydrogen bonding guides the nucleophilic attack, resulting in no label scrambling of the bromoethylamine product. Protein alkylation at cysteine residue with the synthesized Br(13)CH(2)CH(2)NH(2)-HBr is successful. Ab initio calculations in which CH(3)SH serves as a model for the cysteine residue suggest that in gas phase intermolecular attack by the sulfur bearing nucleophile is favored over the intramolecular substitution by the amino group by 15.4 kJ mol(-1). Solution modeling shows that the trend is preserved at basic pH, which is the experimental one, but is reversed at neutral pH. |
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Authors:
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Simona Marincean; Montserrat Rabago Smith; Laci Beltz; Babak Borhan |
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Publication Detail:
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Type: Journal Article Date: 2012-05-29 |
Journal Detail:
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Title: Journal of molecular modeling Volume: 18 ISSN: 0948-5023 ISO Abbreviation: J Mol Model Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-08-29 Completed Date: 2013-01-14 Revised Date: 2013-03-15 |
Medline Journal Info:
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Nlm Unique ID: 9806569 Medline TA: J Mol Model Country: Germany |
Other Details:
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Languages: eng Pagination: 4547-56 Citation Subset: IM |
Affiliation:
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Department of Natural Sciences, University of Michigan-Dearborn, 4901 Evergreen Rd., Dearborn, MI 48128, USA. simonam@umd.umich.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alkylation Cysteine / analogs & derivatives, chemistry, metabolism Ethanolamine / chemistry, metabolism Ethylamines / chemistry, metabolism* Halogenation Magnetic Resonance Spectroscopy Receptors, Retinoic Acid / chemistry, metabolism* Spectrophotometry, Ultraviolet Staining and Labeling* Thermodynamics |
| Chemical | |
Reg. No./Substance:
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0/Ethylamines; 0/Receptors, Retinoic Acid; 0/retinoic acid binding protein II, cellular; 107-09-5/2-bromoethylamine; 141-43-5/Ethanolamine; 2936-69-8/S-2-aminoethyl cysteine; 52-90-4/Cysteine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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