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Photoprotected Peptide α ‐Ketoacids and Hydroxylamines for Iterative and One‐Pot KAHA Ligations: Synthesis of NEDD 8
Author(s) -
Thuaud Frédéric,
Rohrbacher Florian,
Zwicky André,
Bode Jeffrey W.
Publication year - 2016
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.201600264
Subject(s) - chemistry , protecting group , peptide , peptide synthesis , combinatorial chemistry , hydroxylamine , convergent synthesis , solid phase synthesis , chemical ligation , ligation , native chemical ligation , chemical synthesis , biochemistry , organic chemistry , in vitro , alkyl , microbiology and biotechnology , biology
The convergent synthesis of proteins by multiple ligations requires segments protected at the N‐ and/or C‐terminus with masking groups that are orthogonal to the acid‐ and base‐labile protecting groups used in Fmoc‐ SPPS . They must be stable to solid‐phase peptide synthesis, HPLC purification, and ligation conditions and easily removed in the presence of unprotected side chains. In this report, we document photolabile protecting groups for both α ‐ketoacids and hydroxylamines, the key functional groups employed in the α ‐ketoacid–hydroxylamine ( KAHA ) ligation. The novel photoprotected α ‐ketoacid is easily installed onto numerous different C‐terminal peptide α ‐ketoacids and removed by UV light under aqueous conditions. These advances were applied to the one‐pot synthesis of NEDD 8, an important modifier protein, by three different convergent routes. These new protecting groups provide greater flexibility on the order of fragment assembly and reduce the number of reaction and purification steps needed for protein synthesis with the KAHA ligation.