TY  - JOUR
AU  - Hoffmann, S.
AU  - Funke, S. A.
AU  - Wiesehan, K.
AU  - Moedder, S.
AU  - Glück, J.M.
AU  - Feuerstein, S.E.
AU  - Gerdts, J.
AU  - Moetter, J.
AU  - Willbold, D.
TI  - Competitively selected protein ligands pay their increase in specificity by a decrease in affinity
JO  - Molecular BioSystems
VL  - 6
SN  - 1742-206X
CY  - Cambridge
PB  - Royal Society of Chemistry
M1  - PreJuSER-9747
SP  - 126 - 133
PY  - 2010
N1  - Record converted from VDB: 12.11.2012
AB  - Protein-ligand interactions characterise and govern the current state and fate of a living cell. The specificity of proteins is mainly determined by the relative affinities to each potential ligand. To investigate the consequences and potentials of ligands with increased specificity in comparison with ligands optimised solely for affinity, it was necessary to identify ligands that are optimised towards specificity instead of a barely optimised affinity to a given target. In the presented example, a modified phage display screening procedure yielded specific ligands for the LckSH3 domain. We found that increased specificity of one of the hereby obtained ligands for LckSH3 is achieved at the cost of a slightly reduced affinity to LckSH3 and a drastically reduced affinity to other SH3 domains. A surface plasmon resonance experiment simulating in vivo-like realistic competitive binding conditions exerted enhanced binding behaviour of the specific ligand under these binding conditions. The experimental data, together with a mathematical model describing the complex experimental situation, and theoretical considerations lead to the conclusion that increased specificity is achieved at the cost of reduced affinity, but after all, it pays if the ligand is applied under realistic, i.e. competitive, conditions.
KW  - Binding Sites: genetics
KW  - Binding Sites: physiology
KW  - Ligands
KW  - Peptide Library
KW  - Protein Binding
KW  - Proteins: chemistry
KW  - Proteins: metabolism
KW  - Surface Plasmon Resonance
KW  - src Homology Domains: genetics
KW  - src Homology Domains: physiology
KW  - Ligands (NLM Chemicals)
KW  - Peptide Library (NLM Chemicals)
KW  - Proteins (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:20024074
UR  - <Go to ISI:>//WOS:000272875200015
DO  - DOI:10.1039/b910945e
UR  - https://juser.fz-juelich.de/record/9747
ER  -