Synthesis and evaluation of tripodal peptide analogues for cellular delivery of phosphopeptides

Guofeng Ye, Nguyen Hai Nam, Anil Kumar, Ali Saleh, Dinesh B. Shenoy, Mansoor M. Amiji, Xiaofeng Lin, Gongqin Sun, Keykavous Parang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3604-3617
Number of pages14
JournalJournal of Medicinal Chemistry
Volume50
Issue number15
DOIs
StatePublished - Jul 26 2007
Externally publishedYes

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Phosphopeptides
Fluorescein
Peptides
Fluorescence
Phosphotyrosine
Fluorescence Polarization
src Homology Domains
Flow cytometry
Cell membranes
Cytosol
Assays
Flow Cytometry
Cell Membrane
Polarization

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Ye, G., Nam, N. H., Kumar, A., Saleh, A., Shenoy, D. B., Amiji, M. M., ... Parang, K. (2007). Synthesis and evaluation of tripodal peptide analogues for cellular delivery of phosphopeptides. Journal of Medicinal Chemistry, 50(15), 3604-3617. https://doi.org/10.1021/jm070416o

Synthesis and evaluation of tripodal peptide analogues for cellular delivery of phosphopeptides. / Ye, Guofeng; Nam, Nguyen Hai; Kumar, Anil; Saleh, Ali; Shenoy, Dinesh B.; Amiji, Mansoor M.; Lin, Xiaofeng; Sun, Gongqin; Parang, Keykavous.

In: Journal of Medicinal Chemistry, Vol. 50, No. 15, 26.07.2007, p. 3604-3617.

Research output: Contribution to journalArticle

Ye, G, Nam, NH, Kumar, A, Saleh, A, Shenoy, DB, Amiji, MM, Lin, X, Sun, G & Parang, K 2007, 'Synthesis and evaluation of tripodal peptide analogues for cellular delivery of phosphopeptides', Journal of Medicinal Chemistry, vol. 50, no. 15, pp. 3604-3617. https://doi.org/10.1021/jm070416o
Ye, Guofeng ; Nam, Nguyen Hai ; Kumar, Anil ; Saleh, Ali ; Shenoy, Dinesh B. ; Amiji, Mansoor M. ; Lin, Xiaofeng ; Sun, Gongqin ; Parang, Keykavous. / Synthesis and evaluation of tripodal peptide analogues for cellular delivery of phosphopeptides. In: Journal of Medicinal Chemistry. 2007 ; Vol. 50, No. 15. pp. 3604-3617.
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