A new strategy for the preparation of peptide-targeted technetium and rhenium radiopharmaceuticals. The automated solid-phase synthesis, characterization, labeling, and screening of a peptide-ligand library targeted at the formyl peptide receptor

Karin A. Stephenson, Sangeeta Ray, Oyebola O. Sogbein, Murali K. Levadala, Nicole McFarlane, Douglas R. Boreham, Kevin P. Maresca, John W. Babich, Jon Zubieta, John F. Valliant

Research output: Contribution to journalArticle

Abstract

A new solid-phase, synthetic methodology was developed that enables libraries of peptide-based Tc-(I)/Re(I) radiopharmaceuticals to be prepared using a conventional automated peptide synthesizer. Through the use of a tridentate ligand derived from N-α-Fmoc-L-lysine, which we refer to as a single amino acid chelate (SAAC), a series of 12 novel bioconjugates [R-NH(CO)ZLF(SAAC)G, R = ethyl, isopropyl, n-propyl, tert-butyl, n-butyl, benzyl; Z = Met, Nle] that are designed to target the formyl peptide receptor (FPR) were prepared. Construction of the library was carried out in a multiwell format on an Advanced ChemTech 348 peptide synthesizer where multi-milligram quantities of each peptide were isolated in high purity without HPLC purification. After characterization, the library components were screened for their affinity for the FPR receptor using flow cytometry where the Ka values were found to be in the low micromolar range (0.5-3.0 μM). Compound 5j was subsequently labeled with 99mTc(I) and the product isolated in high radiochemical yield using a simple Sep-Pak purification procedure. The retention time of the labeled compound matched that of the fully characterized Re-analogue which was prepared through the use of the same solid-phase synthesis methodology that was used to construct the library. The work reported here is a rare example of a method by which libraries of peptide-ligand conjugates and their rhenium complexes can be prepared.

Original languageEnglish (US)
Pages (from-to)1189-1195
Number of pages7
JournalBioconjugate Chemistry
Volume16
Issue number5
DOIs
StatePublished - Sep 2005
Externally publishedYes

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Formyl Peptide Receptor
Rhenium
Technetium
Peptide Library
Solid-Phase Synthesis Techniques
Radiopharmaceuticals
Labeling
Peptides
Libraries
Screening
Ligands
Purification
Amino Acids
Flow cytometry
Carbon Monoxide
Lysine
Flow Cytometry
Amino acids
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

A new strategy for the preparation of peptide-targeted technetium and rhenium radiopharmaceuticals. The automated solid-phase synthesis, characterization, labeling, and screening of a peptide-ligand library targeted at the formyl peptide receptor. / Stephenson, Karin A.; Ray, Sangeeta; Sogbein, Oyebola O.; Levadala, Murali K.; McFarlane, Nicole; Boreham, Douglas R.; Maresca, Kevin P.; Babich, John W.; Zubieta, Jon; Valliant, John F.

In: Bioconjugate Chemistry, Vol. 16, No. 5, 09.2005, p. 1189-1195.

Research output: Contribution to journalArticle

Stephenson, Karin A. ; Ray, Sangeeta ; Sogbein, Oyebola O. ; Levadala, Murali K. ; McFarlane, Nicole ; Boreham, Douglas R. ; Maresca, Kevin P. ; Babich, John W. ; Zubieta, Jon ; Valliant, John F. / A new strategy for the preparation of peptide-targeted technetium and rhenium radiopharmaceuticals. The automated solid-phase synthesis, characterization, labeling, and screening of a peptide-ligand library targeted at the formyl peptide receptor. In: Bioconjugate Chemistry. 2005 ; Vol. 16, No. 5. pp. 1189-1195.
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AU - Ray, Sangeeta

AU - Sogbein, Oyebola O.

AU - Levadala, Murali K.

AU - McFarlane, Nicole

AU - Boreham, Douglas R.

AU - Maresca, Kevin P.

AU - Babich, John W.

AU - Zubieta, Jon

AU - Valliant, John F.

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