Synthesis and Evaluation of Tripodal Peptide Analogues for Cellular Delivery of Phosphopeptides
Document Type
Article
Publication Date
2007
Abstract
Tripodal peptide analogues were designed on the basis of the phosphotyrosine binding pocket of the Src SH2 domain and assayed for their ability to bind to fluorescein-labeled phosphopeptides. Fluorescence polarization assays showed that a number of amphipathic linear peptide analogues (LPAs), such as LPA4, bind to fluorescein-labeled GpYEEI (F-GpYEEI). LPA4 was evaluated for potential application in cellular delivery of phosphopeptides. Fluorescence microimaging cellular uptake studies with fluorescein-attached LPA4 (F-LPA4) alone or with the mixture of LPA4 and F-GpYEEI in BT-20 cells showed dramatic increase of the fluorescence intensity in cytosol of cells, indicating that LPA4 can function as a delivery tool of F-GpYEEI across the cell membrane. Fluorescent flow cytometry studies showed the cellular uptake of F-LPA4 in an energy-independent pathway and confirmed the cellular uptake of F-GpYEEI in the presence of LPA4. These studies suggest that amphipathic tripodal peptide analogues, such as LPA4, can be used for cellular delivery of phosphopeptides.
Recommended Citation
Ye, Guofeng, Nguyen-Hai Nam, Anil Kumar, Ali Saleh, Dinesh B. Shenoy, Mansoor M. Amiji, Xiaofeng Lin, Gongqin Sun, and Keykavous Parang. "Synthesis and evaluation of tripodal peptide analogues for cellular delivery of phosphopeptides." Journal of medicinal chemistry 50, no. 15 (2007): 3604-3617.
doi: 10.1021/jm070416o
Copyright
American Chemical Society
Comments
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Medicinal Chemistry, volume 50, issue 15, 2007 following peer review. The definitive publisher-authenticated version is available online at DOI: 10.1021/jm070416o.