One-Bead-One-Compound Library of End-Capped Dipeptides and Deconvolution by Microflow NMR.

摘要

As part of our program to identify novel small molecules with interesting biological activity,we have designed and synthesized a library of end-capped dipeptides with an emphasis on compound diversity,complexity,and membrane permeability.An ~1500-member library was synthesized manually on large polystyrene beads using the mix-and-split method.The final compounds were cleaved into 384-well plates to generate individual stock solutions for input into high-throughput biological screens.Individual compounds were decoded using a combination of mass spectrometry and microflow NMR spectroscopy.In principle,this approach to deconvolution obviates the need for complicated binary encoding-decoding strategies for one-bead-one-compound libraries.