ID 111880
Author
Nakamura, Takahiro Tokushima University
Sato, Kohei Tokushima University
Naruse, Naoto Tokushima University
Kitakaze, Keisuke Tokushima University
Hirokawa, Takatsugu AIST
Keywords
native chemical ligation
prolyl thioester
N-sulfanylethylanilide
kinetically-controlled ligation
GM2AP
Content Type
Journal Article
Description
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.
Journal Title
ChemBioChem
ISSN
14397633
NCID
AA11617132
AA11497584
Publisher
WILEY-VCH Verlag GmbH & Co. KGaA
Volume
17
Issue
20
Start Page
1986
End Page
1992
Published Date
2016-08-19
Rights
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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DOI (Published Version)
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language
eng
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departments
Pharmaceutical Sciences