Development of One-Bead Two-Compounds Technology for the Identification of Cell Surface Acting Functional Ligands

摘要

The one-bead-one-compound (OBOC) combinatorial technology [1] allows one to efficiently generate thousands to millions of chemical entities on tiny beads (100 microns), such that each bead displays 10~(13) copies of only one chemical entity. In the last decade, we have successfully used this enabling technology to identify targeting ligands against specific cell surface receptors [2,3] or intracellular proteins. We have modified the OBOC method to a one-bead-twocompounds (OBTC) cell-based screening strategy which enables easy identification of cell surface acting functional molecules. In the OBTC library, every bead has two compounds on its outer layer: (i) a known adhesion ligand for cell binding and (ii) a random library compound constructed with "split-mix" synthesis technique [1]. Screening methods for OBTC libraries to identify cell surface acting signaling ligands are relatively simple, inexpensive, robust and can be easily adapted to academic laboratories.