Abstract

One-bead two-compound (OB2C) combinatorial chemistry libraries enable the discovery of novel synthetic compounds which can be used to evoke specific signaling response in cells. The library configuration is composed of a fixed known cell adhesion ligand and a random chemical library displayed on the surface of Tentagel beads. The cell adhesion ligand binds to specific receptors located on the surface of cells enabling the random immobilized chemical molecules on each bead resin bead to evoke specific cellular responses such as apoptosis or cell death. To validate this concept, a OB2C combinatorial library comprised of an α4β1 integrin targeting ligand, LLP2A, and a novel self-folding tricyclic branched hexamer random library were screened against various hematological and epithelial cancer cell lines: Raji, Molt4, Jurkat, TK6, and PC3N. These cells were incubated with library beads for 48 hours in 6 well tissue culture plates. Propidium iodide, a DNA intercalating agent, is then added to each well to evaluate cell viability. When visualized under a fluorescent microscope, with wavelength excited at 488 nm, cells bound to the OB2C libraries will fluoresce red, indicating apoptosis. From the Raji cell line screening, one bead from the LDO2A-LLP2A library was selected for invoking apoptosis. The morphological appearance of the cells bound to this bead were: blebbing, cell shrinkage, nuclear fragmentation, chromatin fragmentation, and chromosomal DNA fragmentation. Further sequencing via Edman degradation will be performed to identify the amino acid sequence. This chemical approach has the potential to target and kill Burkitt lymphoma.

Disciplines

Alternative and Complementary Medicine | Biochemistry | Medical Cell Biology | Medical Sciences

Mentor

Kit Lam and Mary Saunders

Lab site

Center for Biophotonics Science and Technology (CBST)

Funding Acknowledgement

This material is based upon work supported by the S.D. Bechtel, Jr. Foundation and by the National Science Foundation under Grant No. 0952013. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the S.D. Bechtel, Jr. Foundation or the National Science Foundation.

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URL: http://digitalcommons.calpoly.edu/star/75

 

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