Direct formation and site-selective elaboration of methionine sulfoximine in polypeptides

Sulfoximines are emerging moieties for medicinal and biological chemistry, due in part to their efficacy in selective inhibition of amide-forming enzymes such as γ-glutamylcysteine synthetase. While small-molecule sulfoximines such as methionine sulfoximine (MSO) and its derivatives are well studied...

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Veröffentlicht in:Chemical science (Cambridge) 2022-12, Vol.13 (47), p.1411-1415
Hauptverfasser: Ding, Yuxuan, Pedersen, Simon S, Lin, Alex, Qian, Ruoyu, Ball, Zachary T
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Sprache:eng
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Zusammenfassung:Sulfoximines are emerging moieties for medicinal and biological chemistry, due in part to their efficacy in selective inhibition of amide-forming enzymes such as γ-glutamylcysteine synthetase. While small-molecule sulfoximines such as methionine sulfoximine (MSO) and its derivatives are well studied, structures with methionine sulfoximine residues within complex polypeptides have been generally inaccessible. This paper describes a straightforward means of late-stage one-step oxidation of methionine residues within polypeptides to afford NH-sulfoximines. We also present chemoselective subsequent elaboration, most notably by copper( ii )-mediated N-H cross-coupling at methionine sulfoximine residues with arylboronic acid reagents. This development serves as a strategy to incorporate diverse sulfoximine structures within natural polypeptides, and also identifies the methionine sulfoximine residue as a new site for bioorthogonal, chemoselective bioconjugation. Sulfoximines are emerging moieties for medicinal and biological chemistry. This work describes the late-stage incorporation of methionine sulfoximine residues into polypeptides and chemoselective subsequent elaboration of NH-sulfoximines.
ISSN:2041-6520
2041-6539
DOI:10.1039/d2sc04220g