On-resin N-terminal peptoid degradation: Toward mild sequencing conditions.
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.
Lawrence Berkeley National Laboratory, The Molecular Foundry, 1 Cyclotron Road, Berkeley, California, 94720.
Caroline
C
Proulx
Lawrence Berkeley National Laboratory, The Molecular Foundry, 1 Cyclotron Road, Berkeley, California, 94720.
Falko
F
Noë
Lawrence Berkeley National Laboratory, The Molecular Foundry, 1 Cyclotron Road, Berkeley, California, 94720.
Stan
S
Yoo
Lawrence Berkeley National Laboratory, The Molecular Foundry, 1 Cyclotron Road, Berkeley, California, 94720.
Michael D
MD
Connolly
Lawrence Berkeley National Laboratory, The Molecular Foundry, 1 Cyclotron Road, Berkeley, California, 94720. rnzuckermann@lbl.gov.
Ronald N
RN
Zuckermann
D034444:Peptoids / Q000737:chemistry / Q000235:genetics; D059748:Proteolysis; D020539:Sequence Analysis, Protein / Q000379:methods*
D034444:Peptoids
Edman degradation; N-terminal degradation; peptoid sequencing