Notes and references
{ The method of formation of the HOAT active ester has previously been
shown to affect acylation yields,23 and we therefore tried both DIC and
in situ activation with HATU.
§ UV irradiation was performed using a hand-held UV lamp for thin-layer
chromatography. For details, see experimental procedures{.
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Fig. 3 Photocleavage of 4-methoxy-2-nitrobenzyl-peptide (1 mM) with
cysteine (200 mM) added as a scavenger. The arrow indicates the
deprotected peptide, MGGFL. Cleavage was monitored by RP-HPLC on
a C4 column using a 5–65% gradient of solvent B or solvent A where A =
H2O + 0.1% TFA and B = ACN + 0.08% TFA. Detection was at 214 nm.
cysteine as a scavenger greatly reduced the formation of side-
products during the reaction, and the deprotected peptide was
recovered near quantitatively. Because cysteine is both a natural
and mild scavenger, we expect it to be compatible with photolytic
deprotection of N(2-Nb)-protected peptides in biological contexts.
In this report we have demonstrated the stability of N(2-Nb)
protecting groups to the conditions of Boc chemistry SPPS,
described conditions for the incorporation of N(2-Nb) groups
during peptide synthesis, and optimized photolytic cleavage of
4-methoxy-2-nitrobenzyl from the peptide backbone. We are
currently using 2-Nb as a backbone protecting group to improve
the synthesis and handling of sparingly soluble peptides.
We gratefully acknowledge support from the Department of
Energy Genomes to Life-Genomics Program (Grant DE-FG02-
04ER63786) and the MD/PhD Graduate Training in Growth and
Development program at the University of Chicago (NIH T32
HD007009).
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