Concise site-specific synthesis of DTPA-peptide conjugates: Application to imaging probes for the chemokine receptor CXCR4

Ryo Masuda, Shinya Oishi*, Hiroaki Ohno, Hiroyuki Kimura, Hideo Saji, Nobutaka Fujii

*この研究の対応する著者

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Diethylenetriaminepentaacetic acid (DTPA) is a useful chelating agent for radionuclides such as 68Ga, 99mTc and 111In, which are applicable to nuclear medicine imaging. In this study, we established a facile synthetic protocol for the production of mono-DTPA-conjugated peptide probes. A novel monoreactive DTPA precursor reagent was synthesized in two steps using the chemistry of the o-nitrobenzenesulfonyl (Ns) protecting group, and under mild conditions this DTPA precursor was incorporated onto an N-bromoacetylated Lys of a protected peptide resin. The site-specific DTPA conjugation was facilitated by using a highly acid-labile 4-methyltrityl (Mtt) protecting group for the target site of the bioactive peptide during the solid-phase synthesis. A combination of both techniques yielded peptides with disulfide bonds, such as octreotide and polyphemusin II-derived CXCR4 antagonists. DTPA-peptide conjugates were purified in a single step following cleavage from the resin and disulfide bond formation. This site-specific on-resin construction strategy was used for the design and synthesis of a novel In-DTPA-labeled CXCR4 antagonist, which exhibited highly potent inhibitory activity against SDF-1-CXCR4 binding.

本文言語English
ページ(範囲)3216-3220
ページ数5
ジャーナルBioorganic and Medicinal Chemistry
19
10
DOI
出版ステータスPublished - 2011 5月 15
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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