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Fluorescent Isoindole Crosslink (FlICk) Chemistry: A Rapid, User-friendly Stapling Reaction.
- Source :
-
Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2019 Oct 01; Vol. 58 (40), pp. 14120-14124. Date of Electronic Publication: 2019 Jul 18. - Publication Year :
- 2019
-
Abstract
- The stabilization of peptide secondary structure via stapling is a ubiquitous goal for creating new probes, imaging agents, and drugs. Inspired by indole-derived crosslinks found in natural peptide toxins, we employed ortho-phthalaldehydes to create isoindole staples, thus transforming inactive linear and monocyclic precursors into bioactive monocyclic and bicyclic products. Mild, metal-free conditions give an array of macrocyclic α-melanocyte-stimulating hormone (α-MSH) derivatives, of which several isoindole-stapled α-MSH analogues (K <subscript>i</subscript> ≈1 nm) are found to be as potent as α-MSH. Analogously, late-stage intra-annular isoindole stapling furnished a bicyclic peptide mimic of α-amanitin that is cytotoxic to CHO cells (IC <subscript>50</subscript> =70 μm). Given its user-friendliness, we have termed this approach FlICk (fluorescent isoindole crosslink) chemistry.<br /> (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Details
- Language :
- English
- ISSN :
- 1521-3773
- Volume :
- 58
- Issue :
- 40
- Database :
- MEDLINE
- Journal :
- Angewandte Chemie (International ed. in English)
- Publication Type :
- Academic Journal
- Accession number :
- 31211905
- Full Text :
- https://doi.org/10.1002/anie.201906514