Novel high-affinity binders of human interferon gamma derived from albumin-binding domain of protein G

0385253 - MBÚ 2013 RIV US eng J - Journal Article
Ahmad, Jawid Nazir - Li, J. - Biedermannová, Lada - Kuchař, Milan - Šípová, Hana - Semerádtová, A. - Černý, Jiří - Petroková, Hana - Mikulecký, Pavel - Polínek, Jiří - Staněk, Ondřej - Vondrášek, Jiří - Homola, Jiří - Malý, J. - Osička, Radim - Šebo, Peter - Malý, Petr
Novel high-affinity binders of human interferon gamma derived from albumin-binding domain of protein G.
Proteins-Structure, Function and Bioinformatics. Roč. 80, č. 3 (2012), s. 774-789. ISSN 0887-3585. E-ISSN 1097-0134
R&D Projects: GA AV ČR KAN200520702; GA ČR GAP305/10/2184
Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50520701; CEZ:AV0Z20670512
Keywords : recombinant ligand * protein scaffold * computational design
Subject RIV: CE - Biochemistry
Impact factor: 3.337, year: 2012

Recombinant ligands derived from small protein scaffolds show promise as robust research and diagnostic reagents and next generation protein therapeutics. Here, we derived high-affinity binders of human interferon gamma (hIFN gamma) from the three helix bundle scaffold of the albumin-binding domain (ABD) of protein G from Streptococcus G148. Computational interaction energy mapping, solvent accessibility assessment, and in silico alanine scanning identified 11 residues from the albumin-binding surface of ABD as suitable for randomization. A corresponding combinatorial ABD scaffold library was synthesized and screened for hIFN gamma binders using in vitro ribosome display selection, to yield recombinant ligands that exhibited Kd values for hIFN gamma from 0.2 to 10 nM
Permanent Link: http://hdl.handle.net/11104/0214575