Design of coordination interaction of Zn(II) complex with oligo-aspartate peptide to afford a high-affinity tag-probe pair

Hirokazu Fuchida, Shigekazu Tabata, Naoya Shindo, Ippei Takashima, Qiao Leng, Yuji Hatsuyama, Itaru Hamachi, Akio Ojida

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

A complementary recognition pair consisting of a genetically encodable peptide tag and a small molecular probe isa powerful tool to specifically label and manipulate a protein ofinterest under biological conditions. In this study, we report the redesign of a tag-probe pair comprising an oligo-aspartate peptide tag (such as DDDD) and a binuclear zinc complex. Isothermal-titration calorimetry screening of binding between the series of peptides and zinc complexes revealed that the binding affinity was largely influenced by subtle changes of the ligand structure of the probe. However, the binding was tolerant to differences of the tag peptide sequence. Of those tested, a pair containing a peptide tag (DDAADD) and a binuclear zinc complex possessing 4-chloropyridines (3-2Zn(II)) showed the strongest binding affinity (Ka = 3.88 × 105 M-1), which was about 10-fold larger than the conventional pair of D4-peptide tag (DDDD) and 1-2Zn(II) containing nonsubstituted pyridines (Ka = 3.73 × 104 M-1). The strong binding of this new complementary recognition pair enabled the rapid covalent labeling of a tag-fused maltose binding protein with a fluorescent zinc complex, demonstrating its potential utility in protein analysis.

Original languageEnglish
Pages (from-to)784-791
Number of pages8
JournalBulletin of the Chemical Society of Japan
Volume88
Issue number6
DOIs
Publication statusPublished - Jan 1 2015

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

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