Peptide Macrocyclization Inspired by Non-Ribosomal Imine Natural Products.
J Am Chem Soc
; 139(14): 5233-5241, 2017 Apr 12.
Article
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| MEDLINE
| ID: mdl-28326777
ABSTRACT
A thermodynamic approach to peptide macrocyclization inspired by the cyclization of non-ribosomal peptide aldehydes is presented. The method provides access to structurally diverse macrocycles by exploiting the reactivity of transient macrocyclic peptide imines toward inter- and intramolecular nucleophiles. Reactions are performed in aqueous media, in the absence of side chain protecting groups, and are tolerant of all proteinogenic functional groups. Macrocyclic products bearing non-native and rigidifying structural motifs, isotopic labels, and a variety of bioorthogonal handles are prepared, along with analogues of four distinct natural products. Structural interrogation of the linear and macrocyclic peptides using variable-temperature NMR and circular dichroism suggests that preorganization of linear substrates is not a prerequisite for macrocyclization.
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MEDLINE
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En
Revista:
J Am Chem Soc
Año:
2017
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Article
País de afiliación:
Estados Unidos