Binding Bioassays

The comparison of fish bioassays (6) with the calculated effective doses indicate that the two most potent brevetoxins, PbTx-1 and PbTx-7, also are most effective at displacing tritiated probe from its specific site of action. The considerably lower potency of brevetoxins PbTx-5 and PbTx-6 in the rat system suggest that these two toxins may bind with lesser affinity to site 5. In a general sense, this is indicated in Table II, and is summmarized in Table III. 

A virtual screen of 10,000 primary amine fragments against dipeptidyl peptidase IV (a diabetes target) identified a number of hits, as determined by bioassay screening at 100 pM, e.g. 6 [21]. An X-ray structure of this fragment confirmed the predicted binding mode in the Si pocket and inspired a structure-based hypothesis that eventually led to identification of a potent series of DPP-IV inhibitors [22],... 

Euture improvements of the methods presented here will include modifications that enable determination of the thermodynamic parameters of protein-ligand binding interactions. Eor example, ALIS-based Kd or off-rate measurements at varying temperatures could yield useful relationships between chemical structures and binding thermodynamics. Ready access to such information, especially for targets that otherwise require complex bioassays for their study, could posi-... 

There are numerous advantages to the FAC approach that differentiate it from many forms of bioassay - MS-dependent or otherwise. The FAC method offers thermodynamic and kinetic binding data from the breakthrough curves. As with the classical application of the FA method, the quality of the data is superb relative to other chromatographic or electrophoretic methods [9, 10]. It is an equilibrium method, as opposed to systems that rely upon the separation of bound from unbound, and this forms the basis of its accuracy. 

Rahman, A., Choudhary, M. 1., Thomsen, W. J. Radioligand binding assays, in Bioassay Techniques for Drug Development, ed. Rahman, A., Choudhary, M. 1., Thomsen, W. J., Harwood Academic Publishers, Amsterdam, 2001, pp 179-218. 

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