Extra Binding Interactions
Knowing the structure of the binding site and how the lead compound binds to that site is of enormous help in deciding which functional groups should be added and to which part of the skeleton they should be added. Molecular modeling allows a study of the unused space in the binding site and will indicate whether that space contains hydrophobic or hydrophilic amino acids. Substituents can then be chosen that are capable of fitting and interacting with these regions. Attaching substituents to the carbon skeleton of the molecule is more difficult and usually requires a total synthesis. Moreover, the positions where the new groups can be placed will depend on the synthetic route used and the availability of the necessary reagents. New functional groups could be introduced to different parts of the skeleton depending on the synthesis used and the availability of reagents.