Macromolecular targeting ligands

Fundamentally, FBDD is a general approach aimed at deriving high affinity ligands for macromolecular targets starting from low MW binders, which are usually identified by the use of the aforementioned biophysical techniques [1, 2, 7, 8]. 

Fig. 10.6 Concept of multitarget affinity specificity screening (MASS). Macromolecular targets (typically structured RNA constructs or proteins) in nondenaturing buffers are mixed in solution with a collection of potential ligands derived from natural product fractions, combinatorial libraries, or other diverse compound collections. The...

Design refers to the proposal of a structure in order to achieve the objectives of binding to a macromolecular target site (in the extreme case no ligand may be known), or to achieve the enhancement in potency, the selectivity, the safety and the delivery characteristics that are deemed necessary. 

If a ligand had high affinity for a macromolecular target (as had been shown by classical pharmacological studies over many decades), it should be thermodynamically possible to measure the binding of the ligand to the receptor without... 

In the context of this chapter structure-based design refers to the process of determining the three-dimensional structure of a lead molecule or macromolecular target, or determining the structure of the macromolecule-ligand complex, and using this information to... 

Although the structure of the macromolecule alone is of less interest than that of the complex, in many cases a determination of the structure of the complex follows from earlier studies on the unbound macromolecule. It is thus useful to describe the approaches to structure determination of macromolecular targets. This is followed by a discussion of the dynamic aspects of protein structures in Section 3.2, before addressing the main topic of macromolecule-ligand interactions in Section 3.3. 

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