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.
Abstract
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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https://hdl.handle.net/10161/24959Published Version (Please cite this version)
10.1016/j.bmcl.2022.128725Publication Info
Zhou, Zhengyuan; Zalutsky, Michael R; & Chitneni, Satish 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. Bioorganic & medicinal chemistry letters, 66. pp. 128725. 10.1016/j.bmcl.2022.128725. Retrieved from https://hdl.handle.net/10161/24959.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Satish K. Chitneni
Associate Professor in Radiology
PET radiochemistry and molecular imaging New radiopharmaceutical development for CNS
imaging and cancers Pre-clinical PET/CT imaging
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Michael Rod Zalutsky
Jonathan Spicehandler, M.D. Distinguished Professor of Neuro Oncology, in the School
of Medicine
The overall objective of our laboratory is the development of novel radioactive compounds
for improving the diagnosis and treatment of cancer. This work primarily involves
radiohalo-genation of biomolecules via site-specific approaches, generally via demetallation
reactions. Radionuclides utilized for imaging include I-123, I-124 and F-18, the later
two being of particular interest because they can be used for the quantification of
biochemical and physiological processes in the living huma
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