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On‐resin N ‐terminal peptoid degradation: Toward mild sequencing conditions
Author(s) -
Proulx Caroline,
Noë Falko,
Yoo Stan,
Connolly Michael D.,
Zuckermann Ronald N.
Publication year - 2016
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.22884
Subject(s) - peptoid , chemistry , side chain , hydrolysis , residue (chemistry) , intramolecular force , cationic polymerization , nucleophile , bromide , degradation (telecommunications) , combinatorial chemistry , stereochemistry , polymer chemistry , medicinal chemistry , peptide , organic chemistry , polymer , telecommunications , biochemistry , computer science , catalysis
A novel approach to sequentially degrade peptoid N ‐terminal N ‐(substituted)glycine residues on the solid‐phase using very mild conditions is reported. This method relies on the treatment of resin‐bound, bromoacetylated peptoids with silver perchlorate in THF, leading to an intramolecular cyclization reaction to liberate the terminal residue as a N ‐substituted morpholine‐2,5‐dione, resulting in a truncated peptoid upon hydrolysis and a silver bromide byproduct. Side‐chain functional group tolerance is explored and reaction kinetics are determined. In a series of pentapeptoids possessing variable, non‐nucleophilic side‐chains at the second position (R 2 ), we demonstrate that sequential N ‐terminal degradation of the first two residues proceeds in 87% and 74% conversions on average, respectively. We further demonstrate that the degradation reaction is selective for peptoids, and represents substantial progress toward a mild, iterative sequencing method for peptoid oligomers. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 726–736, 2016.