What happens to binding behavior as a function of polarity, from non-polar (hydrophobic), to weakly polar, to strongly polar ( have a very strong dipole moment), to charged fragments? I imagine that charged fragments, at high concentration, will binding to many charged residues on the surface of the protein. Are the last 2 just avoided as "bad actors"? In which case SPR is the wrong assay technology for this category of molecules? It would imply that you can only add polarity and charge when you've already gotten a high molecular weight binder? How do you get non-polar fragments that are highly soluble? Seems like a contradiction.
General, binding between two molecules is the result of the interaction by charges on both molecules.
The ion-dipole, and ion-induced dipole forces, hydrogen bonding and Van der Waals forces contribute to the interaction charges. As you mention, al kinds of other polarity states will contribute to the interaction by inducing attraction between the molecules or that the molecules repel each other.
The overall charge of a molecules is determined by iso-electric focussing and is called the pI (iso-electric point) at which the compound has no net electrical charge (
). That said, it does not mean that there are no charges at that point!
The charge of a compound is dependent on the environment (pH and salt concentration) and we use this to regenerate (break the interaction) the ligand.
It is not so that only large molecules can have large charges. It totally depends on the composition of the compound.
Proteins in general have pockets with different charges on the outside of the molecule. (
In addition proteins are optimized by nature not to bind to everything they encounter, otherwise all living thing would stop functioning. When you have a promiscous binder, you are in bad luck and have to find some other means of following the inetraction. Suggestings could be ITC or MicroScale Thermophoresis from Nanotemper.
To dissolve a non-polar compound, dissolve it first in a non-polor solution and then dilute in a hydrophobic solution.