Enzymes targetting

MMP inhibitor development constitutes an important branch of research in both academic and industrial settings and advances our knowledge on the structure-function relationship of these enzymes. Targeting... 

AFJr Yapel. Albumin microspheres heat and chemical stabilization. In KJ Widder, R Green, eds. Methods in Enzymology Part A, Drug and Enzyme Targeting. Orlando Academic Press, 1985, pp 3-18. 

As we have just seen, the initial encounter complex between an enzyme and its substrate is characterized by a reversible equilibrium between the binary complex and the free forms of enzyme and substrate. Hence the binary complex is stabilized through a variety of noncovalent interactions between the substrate and enzyme molecules. Likewise the majority of pharmacologically relevant enzyme inhibitors, which we will encounter in subsequent chapters, bind to their enzyme targets through a combination of noncovalent interactions. Some of the more important of these noncovalent forces for interactions between proteins (e.g., enzymes) and ligands (e.g., substrates, cofactors, and reversible inhibitors) include electrostatic interactions, hydrogen bonds, hydrophobic forces, and van der Waals forces (Copeland, 2000). 

Most drugs bind to their enzyme target through reversible interactions. 

Drug/Candidate Enzyme Target Disease Indication... 

The goal of most HTS assays for enzyme targets is to identify library components that act as inhibitors of enzymatic activity. To identify and compare inhibitory compounds, we must first define a metric that reflects the ability of a fixed concentration of compound to reduce the activity of the target enzyme. The most commonly used metric for this purpose is the inhibition percentage, which can be defined as follows ... 

Compound or Compound Class Enzyme Target Clinical Indication... 

D Fleisher, BH Stewart, GL Amidon. Design of prodrugs for improved GI absorption by intestinal enzyme targeting. Methods Enzymol 112 360-381, 1985. 

In the field of responsive agents, enzyme targeting has specific advantages. A small concentration of the enzyme can convert a relatively high amount of the probe in multiple catalytic cycles which considerably decreases the detection limit for the enzyme as compared to other biomolecules. Moreover, enzymatic reactions are usually highly specific therefore, the observed change... 

---