Combination of Thiol-Additive-Free Native Chemical Ligation/Desulfurization and Intentional Replacement of Alanine with Cysteine.
We report a novel strategy for native chemical ligation (NCL). Alanines not located at a ligation site are temporarily replaced with cysteines, and this enables efficient thiol-additive-free NCL, with subsequent desulfurization to regenerate the target peptide. We synthesized stresscopin-related peptide and neuroendocrine regulatory peptide-2 (NERP-2) by this method. We confirmed that both conventional alkyl thioester and thioester-equivalent N-acyl-N'-methyl-benzimidazolinone (MeNbz) can be adopted as thioester components for thiol-additive-free NCL of multi-Cys-containing peptides.
Peptide Institute, Inc., Saito asagi, Ibaraki-shi, Osaka, 567-0085, Japan.
Shugo
S
Tsuda
Peptide Institute, Inc., Saito asagi, Ibaraki-shi, Osaka, 567-0085, Japan.
Masayoshi
M
Mochizuki
Peptide Institute, Inc., Saito asagi, Ibaraki-shi, Osaka, 567-0085, Japan.
Hideki
H
Nishio
Peptide Institute, Inc., Saito asagi, Ibaraki-shi, Osaka, 567-0085, Japan.
Taku
T
Yoshiya
D000409:Alanine / Q000737:chemistry*; D000595:Amino Acid Sequence; D001562:Benzimidazoles / Q000737:chemistry; D003346:Corticotropin-Releasing Hormone / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D054832:Urocortins / Q000737:chemistry
D001562:Benzimidazoles; D009419:Nerve Tissue Proteins; D010455:Peptides; D013438:Sulfhydryl Compounds; C426704:UCN3 protein, human; D054832:Urocortins; C523895:neuroendocrine regulatory peptide-2, human; C014353:benzimidazolone; D003346:Corticotropin-Releasing Hormone; D003545:Cysteine; D000409:Alanine
desulfurization; native chemical ligation; peptides; synthesis design; thioester; thiol additive free