title: Development of a sufficiently reactive thioalkylester involving the side-chain thiol of cysteine applicable for kinetically controlled ligation.
abstract: N(α) -Trifluoroacetyl-Cys-Leu-NH2 (TfaC-Leu-NH2 ) was incorporated into thioesters through its side-chain thiol group to develop a more reactive peptide-thioester than the commonly used peptide-3-mercaptopropionic acid (MPA)-thioester. The TfaC-thioester could be readily synthesized by solid-phase peptide synthesis (SPPS) with Boc chemistry using in situ neutralization protocols in sufficient yield without any side reaction associated with the use of TfaC. This thioester proved to display a much higher reactivity in the thiol-free native chemical ligation (NCL) reaction than the MPA-thioester and to be comparable to the thioarylester, such as the 4-mercaptophenylacetic acid (MPAA)-thioester, in terms of the ligation rate. We were able to demonstrate the usefulness of the TfaC-thioester by using it to synthesize neuromedin S via a one-pot sequential NCL approach followed by desulfurization. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 503-511, 2016.
authors.affiliation: Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Tsuda
authors.affiliation: Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mochizuki
authors.affiliation: Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan.|Graduate School of Science, Osaka University, Toyonaka, Osaka, 560-0043, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishio
authors.affiliation: Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Yoshiya
authors.affiliation: Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nishiuchi
mesh_terms: D009479:Neuropeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D009479:Neuropeptides; D013438:Sulfhydryl Compounds; C497950:neuromedin S
keywords: TfaC-thioester; kinetically contorolled ligation; thioalkylester