Beyond cysteine: recent developments in the area of targeted covalent inhibition
Over the past decade targeted covalent inhibitors have undergone a renaissance due to the clinical validation and regulatory approval of several small molecule therapeutics that are designed to irreversibly modify their target protein. Invariably, these compounds rely on the serendipitous placement...
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| Veröffentlicht in: | Current opinion in chemical biology 2018-06, Vol.44, p.30-38 |
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| container_title | Current opinion in chemical biology |
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| creator | Mukherjee, Herschel Grimster, Neil P |
| description | Over the past decade targeted covalent inhibitors have undergone a renaissance due to the clinical validation and regulatory approval of several small molecule therapeutics that are designed to irreversibly modify their target protein. Invariably, these compounds rely on the serendipitous placement of a cysteine residue proximal to the small molecule binding site; while this strategy has afforded numerous successes, it necessarily limits the number of proteins that can be targeted by this approach. This drawback has led several research groups to develop novel methodologies that target non-cysteine residues for covalent modification. Herein, we survey the current literature of warheads that covalently modify non-cysteine amino acids in proteins. |
| doi_str_mv | 10.1016/j.cbpa.2018.05.011 |
| format | Article |
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| ispartof | Current opinion in chemical biology, 2018-06, Vol.44, p.30-38 |
| issn | 1367-5931 1879-0402 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Amino Acids - chemistry Amino Acids - metabolism Animals Cysteine - chemistry Cysteine - metabolism Drug Discovery - methods Humans Molecular Targeted Therapy - methods Pharmacology Protein Conformation - drug effects Proteins - antagonists & inhibitors Proteins - chemistry Proteins - metabolism |
| title | Beyond cysteine: recent developments in the area of targeted covalent inhibition |
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