Nakamura, Takahiro Tokushima University
Sato, Kohei Tokushima University
Naruse, Naoto Tokushima University
Kitakaze, Keisuke Tokushima University
Inokuma, Tsubasa Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Hirokawa, Takatsugu AIST
Itoh, Kohji Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Otaka, Akira Tokushima University Tokushima University Educator and Researcher Directory KAKEN Search Researchers
native chemical ligation
A synthetic protocol has been developed for the preparation of 162-residue S-monoglycosylated GM2-activator protein (GM2AP) analogues bearing various amino acid substitutions for Thr69. The facile incorporation of the replacements into the protein was achieved by a one-pot/N–to–C-directed sequential ligation strategy using readily accessible middle N-sulfanylethylanilide (SEAlide) peptides consisting of seven amino acid residues. A kinetically-controlled ligation protocol was successfully applied to the assembly of three peptide segments covering the GM2AP. The native chemical ligation (NCL) reactivities of the SEAlide can be tuned by the presence or absence of phosphate salts. Furthermore, the NCL of the alkyl thioester fragment (GM2AP (1–31)) with the N-terminal cysteinyl prolyl thioester (GM2AP (32–67)) proceeded smoothly to yield the 67-residue prolyl thioester, with the prolyl thioester moiety remaining intact. This newly developed strategy enabled the facile synthesis of GM2AP analogues. Thus, we refered this synthetic protocol as “Tailored Synthesis” for the construction of a GM2AP library.
WILEY-VCH Verlag GmbH & Co. KGaA
This is the peer-reviewed version of the following article: T. Nakamura, K. Sato, N. Naruse, K. Kitakaze, T. Inokuma, T. Hirokawa, A. Shigenaga, K. Itoh, A. Otaka (2016), Tailored Synthesis of 162‐Residue S‐Monoglycosylated GM2‐Activator Protein (GM2AP) Analogues that Allows Facile Access to a Protein Library. ChemBioChem Vol.17 Issue20 p 1986-1992 doi:10.1002/cbic.201600400, which has been published in final form at https://doi.org/10.1002/cbic.201600400.
This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-Archiving.
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