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A Tandem In Situ Peptide Cyclization through Trifluoroacetic Acid Cleavage
Author(s) -
Chandra Koushik,
Roy Tapta Kanchan,
Shalev Deborah E.,
Loyter Abraham,
Gilon Chaim,
Gerber R. Benny,
Friedler Assaf
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201402789
Subject(s) - chemistry , trifluoroacetic acid , succinimide , linker , peptide , peptide bond , combinatorial chemistry , cyclic peptide , peptide synthesis , solid phase synthesis , cleavage (geology) , molecule , side chain , amide , in situ , tandem , stereochemistry , organic chemistry , biochemistry , materials science , fracture (geology) , composite material , polymer , geotechnical engineering , computer science , engineering , operating system
Abstract We present a new approach for peptide cyclization during solid phase synthesis under highly acidic conditions. Our approach involves simultaneous in situ deprotection, cyclization and trifluoroacetic acid (TFA) cleavage of the peptide, which is achieved by forming an amide bond between a lysine side chain and a succinic acid linker at the peptide N‐terminus. The reaction proceeds via a highly active succinimide intermediate, which was isolated and characterized. The structure of a model cyclic peptide was solved by NMR spectroscopy. Theoretical calculations support the proposed mechanism of cyclization. Our new methodology is applicable for the formation of macrocycles in solid‐phase synthesis of peptides and organic molecules.