Synthesis and screening of a library of Re/Tc-based amyloid probes derived from β-breaker peptides

Karin A. Stephenson, Leslie C. Reid, Jon Zubieta, John W. Babich, Mei Ping Kung, Hank F. Kung, John F. Valliant

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Through the development and application of a unique approach for producing Re-metallopeptides, a new class of peptide-derived probes that are designed to target β-amyloid plaques was developed. Derivatives of a class of β-breaker peptides having the core sequence lvffa or affvl (lower case letters represent D-amino acids) and the single amino acid chelate quinoline (SAACQ) ligand which can bind Re and 99mTc were prepared on an automated peptide synthesizer. Both monomeric and dimeric peptides were synthesized in modest to good yields where in select examples a biotin-containing amino acid derivative was included to act as a linker point for further conjugation to carrier proteins. The Re complexes for all reported peptides were prepared similarly and screened for their ability to inhibit fibrillogenesis. Two of the reported compounds showed excellent inhibitory properties (8a: 40 ± 5% amyloid formation versus control; 16: 40 ± 4%) and warrant further investigation. For one of these leads, the 99mTc analogue was synthesized and the product showed high stability toward histidine and cysteine challenges, making it a viable candidate for in vivo biodistribution studies.

Original languageEnglish (US)
Pages (from-to)1087-1094
Number of pages8
JournalBioconjugate Chemistry
Volume19
Issue number5
DOIs
StatePublished - May 1 2008

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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    Stephenson, K. A., Reid, L. C., Zubieta, J., Babich, J. W., Kung, M. P., Kung, H. F., & Valliant, J. F. (2008). Synthesis and screening of a library of Re/Tc-based amyloid probes derived from β-breaker peptides. Bioconjugate Chemistry, 19(5), 1087-1094. https://doi.org/10.1021/bc800001g