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Stapled peptides as scaffolds for developing radiotracers for intracellular targets: Preliminary evaluation of a radioiodinated MDM2-binding stapled peptide in the SJSA-1 osteosarcoma model.

Publication ,  Journal Article
Zhou, Z; Zalutsky, MR; Chitneni, SK
Published in: Bioorg Med Chem Lett
June 15, 2022

Stapled peptides are promising scaffolds for inhibiting protein-protein interactions in cells, including between the intracellular oncoprotein MDM2 and p53. Herein, we have investigated the potential utility of a stapled peptide, VIP116, for developing radiolabeled agents targeting MDM2. VIP116 was radioiodinated using the prosthetic agent N-succinimidyl-3-[*I]iodobenzoate ([*I]SIB). The resulting labeled peptide [*I]SIB-VIP116 exhibited high uptake (165.3 ± 27.7%/mg protein) and specificity in SJSA-1 tumor cells. Tissue distribution studies of [*I]SIB-VIP116 revealed a peak tumor uptake of 2.19 ± 0.56 percent injected dose per gram (%ID/g) in SJSA-1 xenografts at 2 h post-injection, which was stable until 6 h. [*I]SIB-VIP116 exhibited high activity (8.33 ± 1.18%ID/g) in the blood pool but had high tumor-to-muscle ratios (12.0 ± 5.7), at 30 min. Metabolic stability studies in mice indicated that about 80% of the activity in plasma was intact [*I]SIB-VIP116 at 4 h. Our results confirm the cell permeability and specific binding of [*I]SIB-VIP116 to MDM2 and the suitability of the VIP116 scaffold for radiolabeled probe development.

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Published In

Bioorg Med Chem Lett

DOI

EISSN

1464-3405

Publication Date

June 15, 2022

Volume

66

Start / End Page

128725

Location

England

Related Subject Headings

  • Proto-Oncogene Proteins c-mdm2
  • Peptides
  • Osteosarcoma
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Bone Neoplasms
  • Animals
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry
 

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Zhou, Z., Zalutsky, M. R., & Chitneni, S. K. (2022). Stapled peptides as scaffolds for developing radiotracers for intracellular targets: Preliminary evaluation of a radioiodinated MDM2-binding stapled peptide in the SJSA-1 osteosarcoma model. Bioorg Med Chem Lett, 66, 128725. https://doi.org/10.1016/j.bmcl.2022.128725
Zhou, Zhengyuan, Michael R. Zalutsky, and Satish K. Chitneni. “Stapled peptides as scaffolds for developing radiotracers for intracellular targets: Preliminary evaluation of a radioiodinated MDM2-binding stapled peptide in the SJSA-1 osteosarcoma model.Bioorg Med Chem Lett 66 (June 15, 2022): 128725. https://doi.org/10.1016/j.bmcl.2022.128725.
Journal cover image

Published In

Bioorg Med Chem Lett

DOI

EISSN

1464-3405

Publication Date

June 15, 2022

Volume

66

Start / End Page

128725

Location

England

Related Subject Headings

  • Proto-Oncogene Proteins c-mdm2
  • Peptides
  • Osteosarcoma
  • Mice
  • Medicinal & Biomolecular Chemistry
  • Humans
  • Bone Neoplasms
  • Animals
  • 3405 Organic chemistry
  • 3404 Medicinal and biomolecular chemistry