Global transformation of OBOC combinatorial peptide libraries into OBOC polyamine and small molecule libraries.
In "one-bead-one-compound" (OBOC) combinatorial chemistry, a compound-bead library with hundreds of thousands to millions of diversities can be rapidly generated such that each bead displays only one chemical entity. The highly efficient "libraries-from-libraries" approach involves the global transformation of a peptide library into many small molecule solution-phase mixture libraries, but this approach has never been successfully applied to OBOC libraries. Here we report a novel approach that allows us to combine these two enabling technologies to efficiently generate OBOC encoded small molecule bead libraries. By using a topologically segregated bilayer bead and a "ladder-synthesis" method, we can prepare peptide libraries with the peptide on the bead surface and a series of peptide ladders in the bead interior. Various global transformation reactions can then be employed to transform the starting peptide library into a variety of peptidomimetic libraries. During the transformation reactions, the peptide ladders in the bead interior are also transformed in a predictable manner. As a result, individual compound bead can be decoded by analyzing the hydrogen fluoride-released encoding tags with matrix-assisted laser desorption ionization Fourier transform mass spectrometry. Using this novel approach, a random encoded dipeptide library was prepared and subsequently transformed into polyamine and poly- N-acetylamine sublibraries. Random beads isolated from these sublibraries were reliably decoded.
Kappel
Joseph C
JC
Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis Cancer Center, 4501 X Street, Sacramento, California 95817, USA.
Fan
Yi C
YC
Lam
Kit S
KS
D020650:Combinatorial Chemistry Techniques; D013058:Mass Spectrometry; D019151:Peptide Library; D011073:Polyamines / Q000737:chemistry*
D019151:Peptide Library; D011073:Polyamines