Document Detail

A diversity optimized combinatorial library for the identification of Fc-fragment binding ligands.
MedLine Citation:
PMID:  20225303     Owner:  NLM     Status:  MEDLINE    
To generate a library covering a relatively wide area of the chemical space, molecular descriptors, and multivariate data analysis were combined to select the building blocks required for generating a diversity optimized library of putative Fc-fragment binding ligands. In such a method of library design, structural information about the target protein is not needed. Synthesis of the resulting 770 member virtual library was carried out using encoded beads, which facilitated rapid identification of the subsequent hits. The library was screened in an on-bead fluorescence assay with immunoglobulin G Fc-fragment of the subtype 4 to identify Fc-fragment binding ligands that would be useful for purifying monoclonal antibodies. An analysis of the positions of the hits in the chemical space revealed that the ones with the highest fluorescence were primarily concentrated in a particular part of the chemical space. One of the identified hits, when immobilized on amino sepharose, was able to purify a monoclonal antibody from crude cell supernatant with purity of 84% and a 70% recovery. The chemometric tools employed for the library design allowed the identification of the fraction of the available chemical space that would be preferred for a second generation library.
Anders L Nielsen; Flemming S J?rgensen; Lars Olsen; S?ren F Christensen; Andrew J Benie; Thomas Bj?rnholm; Phaedria M St Hilaire
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biopolymers     Volume:  94     ISSN:  0006-3525     ISO Abbreviation:  Biopolymers     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-23     Completed Date:  2010-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372525     Medline TA:  Biopolymers     Country:  United States    
Other Details:
Languages:  eng     Pagination:  192-205     Citation Subset:  IM    
Department of Affinity Purification Technology, Novo Nordisk A/S, Novo Nordisk Park, DK-2760 M?l?v, Denmark.
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MeSH Terms
Combinatorial Chemistry Techniques / classification,  methods
Databases, Protein
Gas Chromatography-Mass Spectrometry
Immunoglobulin Fc Fragments / chemistry*
Molecular Structure
Peptides / analysis
Proteomics / methods
Reg. No./Substance:
0/Immunoglobulin Fc Fragments; 0/Ligands; 0/Peptides

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