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1.
Chem Commun (Camb) ; 47(4): 1309-11, 2011 Jan 28.
Article in English | MEDLINE | ID: mdl-21063592

ABSTRACT

In this paper we describe a highly effective surface modification of SU-8 microparticles, the attachment of appropriate linkers for solid-supported synthesis, and the successful chemical modification of these particles via controlled multi-step organic synthesis leading to molecules attached in an unambiguous manner to the support surface.

2.
Nat Chem Biol ; 5(3): 154-6, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19151731

ABSTRACT

Small-molecule inhibition of extracellular proteins that activate membrane receptors has proven to be extremely challenging. Diversity-oriented synthesis and small-molecule microarrays enabled the discovery of robotnikinin, a small molecule that binds the extracellular Sonic hedgehog (Shh) protein and blocks Shh signaling in cell lines, human primary keratinocytes and a synthetic model of human skin. Shh pathway activity is rescued by small-molecule agonists of Smoothened, which functions immediately downstream of the Shh receptor Patched.


Subject(s)
Hedgehog Proteins/metabolism , Lactams/pharmacology , Lactones/pharmacology , Signal Transduction/drug effects , 3T3 Cells , Animals , Drug Discovery , Humans , Keratinocytes/drug effects , Keratinocytes/metabolism , Lactams/metabolism , Lactones/metabolism , Mice , Patched Receptors , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolism
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