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abstract Tushar Satav

A Supramolecular System to Induce Growth Factor Signaling

Abstract :

Cell surface receptors plays very important role in monitoring extracellular functions as well as coordinating intracellular events via collection, compilation and translation of external information [1]. Most of the growth factors present in cell environment also ellicit their activity via these surface receptors [2]. Multivalent ligands are reported to induce the clustering of these receptors to trigger the localized activation of growth factors which are otherwise highly diffusible and difficult to segregate in In vivo conditions [3].

With the advances in surface fabrication techniques different ligands can be fabricated on the surface to gain spatial and temporal control over growth factor activity known as “preorganization of growth factor” [4] [5]. Moreover electrochemical stimulus can also be used to ellicit the localized response of growth factor [6] [7].

Herein we presented dendrimer functionalized nano-platforms to preorganize the VEGF mediated bio signaling complex on molecular print board via non covalent host guest interactions. Recently a peptide sequence (EYPD) is reported which is specific for α9β1 integrin receptors known to involve in eliciting VEGF activity [8]. Thus we hypothesized that if we present this peptide in a multivalent fashion we will be able to cluster these integrin receptors which will act as a trigger for recruitment of VEGF at these clustered sites. We envisioned that this multivalency can also help to stabilize this construct on β-CD monolayer (molecular print board) by host guest interactions between tyrosine present in peptide and cup shaped β-CD molecules.

Moreover this supramolecular fabrication technique gave us an unique access whereby modifying dendrimer design, we were able to tune the affinity of dendrimers with molecular print board.

References

[1] L. L. Kiessling, J. E. Gestwicki, L. E. Strong, Angewandte Chemie International Edition 2006, 45, 2348-2368.

[2] J. Taipale, J. Keski-Oja, The FASEB Journal 1997, 11, 51-59.

[3] B. R. Griffith, B. L. Allen, A. C. Rapraeger, L. L. Kiessling, Journal of the American Chemical Society 2004, 126, 1608-1609.

[4] M. D. Mager, V. LaPointe, M. M. Stevens, Nat Chem 2011, 3, 582-589.

[5] L. Li, J. R. Klim, R. Derda, A. H. Courtney, L. L. Kiessling, Proceedings of the National Academy of Sciences 2011.

[6] Q. An, J. Brinkmann, J. Huskens, S. Krabbenborg, J. de Boer, P. Jonkheijm, Angewandte Chemie International Edition 2012, 51, 12233-12237.

[7] A. Herland, K. M. Persson, V. Lundin, M. Fahlman, M. Berggren, E. W. H. Jager, A. I. Teixeira, Angewandte Chemie International Edition 2011, 50, 12529-12533.

[8] S. Oommen, S. K. Gupta, N. E. Vlahakis, Journal of Biological Chemistry 2011, 286, 1083-1092.