Induced cytotoxicity of peptides by intracellular native chemical ligation

Abstract

The native chemical ligation (NCL) is a reaction between a pair of peptides, one with a cysteine unit at the N-terminal and the other with a thioester functional group at...

Induced cytotoxicity of peptides with crypto-thioester through native chemical ligation

“…The Hnb moiety was conjugated onto the resin according to a reported procedure. 6,20,24 Briefly, in a DMF/ MeOH/AcOH mixed solvent (44.5 : 44.5 : 1, v/v/v), the resin without the Fmoc protecting group was mixed with 2-hydroxy-5nitrobenzaldehyde (10 equiv.). After 5 min of shaking, the resulting resin was washed with DMF/MeOH (1 : 1, v/v) three times for 5 s each time, and with DMF (5 s, three times).…”

“…In addition, C-terminal crypto-thioesters with N-Hnb-Cys units protected by t-Bu-SH (KLA-C-1 and KLA-C-2) and an N-terminal cysteine unit protected by a disulfidecontaining peptide ligand (KLA-T-1 and KLA-T-2) were introduced into the two pairs of peptide fragments, respectively. Because the cytotoxicity of amphiphilic helical peptides is generally proportional to the helicity and length of the peptide, [18][19][20] these peptide fragments will exhibit low cytotoxicity. In a reducing environment, the protecting groups of these fragments will be removed to form fragments having Nterminal cysteine with free thiol groups and C-terminal thioester units, respectively.…”