Protein hydrophobic ligands

Liu, L. and Klassen, J.S. (2008) Quantifying protein-hydrophobic ligand interactions by ES-MS. Proc. 56th ASMS Conference on Mass Spectrometry and Allied Topics, June 1-5, Denver, CO. 

In an extensive SFA study of protein receptor-ligand interactions, Leckband and co-workers [114] showed the importance of electrostatic, dispersion, steric, and hydrophobic forces in mediating the strong streptavidin-biotin interaction. Israelachvili and co-workers [66, 115] have measured the Hamaker constant for the dispersion interaction between phospholipid bilayers and find A = 7.5 1.5 X 10 erg in water. 

Both the protein and the ligand are solvated by water when they are separated. As the two surfaces interact, water is excluded, hydrogen bonds are broken and formed, hydrophobic interactions occur, and the protein and ligand stick to each other. As in protein folding and for the same reasons, the hydrophobic interaction provides much of the free energy for the association reaction, but polar groups that are removed... 

One limitation of NMR-based screening is the requirement that large protein quantities should yield concentrations giving reasonable durations of NMR experiments and reasonable throughput. Another limitation arises from low solubility (pM) of nondeveloped lead structures. Hydrophobic ligands are often required to enable binding to a hydrophobic... 

Hydrophobic Proteins and peptides differ from one another in their hydrophobic properties. Salt solutions are used to mediate the binding of molecules to a hydrophobic matrix substituted with a hydrophobic ligand. 

The most commonly used hydrophobic marker of hepatic insufficiency is uncon-jngated bilirubin (K= 10 xM" ), which is tightly bonnd to HSA. If one could learn how to remove it effectively from HSA nsing carbonic sorbents, then these sorbents could be applied for removing other protein-bonnd ligands as well. Generally, bilirubin as a free molecule is efficiently adsorbed by activated carbons, bnt in the presence of a competing liquid sorbent HSA, the carbon capacity for bilirnbin falls drastically (Fig. 29.1). 

Adipocyte lipid-binding protein (ALBP) is the adipocyte member of an intracellular hydrophobic ligand-binding protein family. ALBP is phosphorylated by the insulin receptor kinase upon insulin stimulation. The crystal structure of recombinant murine ALBP has been determined and refined to 2.5 A. The final R-factorfor the model is 0.18 with good canonical properties. 

Rothemund S., Liou Y. C., Davies P. L., Krause E. and Sonnichsen E D. (1999) A new class of hexahelical insect proteins revealed as putative carriers of small hydrophobic ligands. Structure Fold Des. 7, 1325-1332. 

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