In vivo tumor imaging using polo-box domain of polo-like kinase 1 targeted peptide

Abstract Polo-like kinase 1 (Plk1) is a regulator of cell cycle progression during mitosis; it is overexpressed in many different tumors and has been implicated as a potential antimitotic target. Plks are characterized by the presence of a highly conserved C-terminal polo-box domain (PBD) that is in...

Full description

Saved in:
Bibliographic Details
Published in:Biomaterials 2012-10, Vol.33 (29), p.6915-6925
Main Authors: Kim, Sung-Min, Yoon, Sunmi, Choi, Naeun, Hong, Kwan Soo, Murugan, Ravichandran N, Cho, Gyunggoo, Ryu, Eun Kyoung
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Antineoplastic Agents - pharmacology
Apoptosis
Cell Cycle Proteins - chemistry
Cell Line, Tumor
Cell Proliferation
Cell Separation
cRGDyK-S-S-CPLHSpT
Dentistry
Drug delivery
Drug Delivery Systems
Flow Cytometry
HeLa Cells
Humans
Male
Mice
Mice, Inbred BALB C
Mitosis
Models, Chemical
Molecular imaging
Neoplasm Transplantation
Neoplasms - diagnosis
Neoplasms - metabolism
Neoplasms - pathology
Peptides - chemistry
PET
Polo-box domain
Polo-Like Kinase 1
Positron-Emission Tomography - methods
Protein Serine-Threonine Kinases - chemistry
Protein Structure, Tertiary
Proto-Oncogene Proteins - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract Polo-like kinase 1 (Plk1) is a regulator of cell cycle progression during mitosis; it is overexpressed in many different tumors and has been implicated as a potential antimitotic target. Plks are characterized by the presence of a highly conserved C-terminal polo-box domain (PBD) that is involved in regulating kinase activity. The phosphopeptide Pro-Leu-His-Ser-p-Thr (PLHSpT) is a potent selective inhibitor of the PBD of human plk1 that acts by inducing mitotic arrest and apoptotic cell death in cancer cells. We synthesized cRGDyK-S-S-CPLHSpT to exploit the drug delivery and molecular imaging using positron emission tomography (PET). The peptide was blocked dramatically proliferation of tumor in vitro and in vivo. It was attempted to develop and show a tumor PET image with the radiolabeled-peptide. Here we showed the peptide is promising not only as an anticancer drug, but also as a radioligand for tumor diagnosis with PET. We expect that our contribution will provide new insights into the design of Plk1 peptide inhibitors and have significant implications for anticancer therapy and tumor diagnosis.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.06.046