Encoded self-assembling chemical libraries

被引:275
作者
Melkko, S [1 ]
Scheuermann, J [1 ]
Dumelin, CE [1 ]
Neri, D [1 ]
机构
[1] Swiss Fed Inst Technol, Dept Chem & Appl Chem, CH-8057 Zurich, Switzerland
关键词
D O I
10.1038/nbt961
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The isolation of molecules capable of high-affinity and specific binding to biological targets is a central problem in chemistry, biology and pharmaceutical sciences. Here we describe the use of encoded self-assembling chemical (ESAC) libraries for the facile identification of molecules that bind macromolecular targets. ESAC technology uses libraries of organic molecules linked to individual oligonucleotides that mediate the self-assembly of the library and provide a code associated with each organic molecule. After panning ESAC libraries on the biomolecular target of interest, the 'binding code' of the selected compounds can be 'decoded' by a number of experimental techniques (e. g., hybridization on oligonucleotide microarrays). The potential of this technology was demonstrated by the affinity maturation (>40-fold) of binding molecules to human serum albumin and bovine carbonic anhydrase, leading to binders with dissociation constants in the nanomolar range.
引用
收藏
页码:568 / 574
页数:7
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