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

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3216-3220
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number10
DOIs
Publication statusPublished - 2011 May 15
Externally publishedYes

Fingerprint

Chemokine Receptors
Imaging techniques
Peptides
Acids
Resins
Disulfides
Nuclear medicine
Solid-Phase Synthesis Techniques
Octreotide
Nuclear Medicine
Chelating Agents
Radioisotopes

Keywords

  • CXCR4
  • DTPA
  • Molecular imaging

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Concise site-specific synthesis of DTPA-peptide conjugates : Application to imaging probes for the chemokine receptor CXCR4. / Masuda, Ryo; Oishi, Shinya; Ohno, Hiroaki; Kimura, Hiroyuki; Saji, Hideo; Fujii, Nobutaka.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 10, 15.05.2011, p. 3216-3220.

Research output: Contribution to journalArticle

Masuda, Ryo ; Oishi, Shinya ; Ohno, Hiroaki ; Kimura, Hiroyuki ; Saji, Hideo ; Fujii, Nobutaka. / Concise site-specific synthesis of DTPA-peptide conjugates : Application to imaging probes for the chemokine receptor CXCR4. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 10. pp. 3216-3220.
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