Back to Search
Start Over
Phosphopeptides with improved cellular uptake properties as ligands for the polo-box domain of polo-like kinase 1
- Source :
-
Bioorganic & Medicinal Chemistry Letters . Aug2011, Vol. 21 Issue 16, p4686-4689. 4p. - Publication Year :
- 2011
-
Abstract
- Abstract: Human polo-like kinase 1 (Plk1) is involved in cell proliferation and overexpressed in a broad variety of different cancer types. Due to its crucial role in cancerogenesis Plk1 is a potential target for diagnostic and therapeutic applications. Peptidic ligands can specifically interact with the polo-box domain (PBD) of Plk1, a C-terminal located phosphoepitope binding motif. Recently, phosphopeptide MQSpTPL has been identified as ligand with high binding affinity. However, a radiolabeled version of this peptide showed only insufficient cellular uptake. The present study investigated peptide dimers consisting of PBD-targeting phosphopeptide MQSpTPL and a cell-penetrating peptide (CPP) moiety. The new constructs demonstrate superior uptake in different cancer cell-lines compared to the phosphopeptide alone. Furthermore, we could demonstrate binding of phosphopeptide-CPP dimers to PBD of Plk1 making the compounds interesting leads for the development of molecular probes for imaging Plk1 in cancer. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0960894X
- Volume :
- 21
- Issue :
- 16
- Database :
- Academic Search Index
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Publication Type :
- Academic Journal
- Accession number :
- 63561099
- Full Text :
- https://doi.org/10.1016/j.bmcl.2011.06.103