Structure Based Design of Non-Peptide Mimetics

The field of systematic structure-based drug design is becoming more promising along with the continuous developments in molecular modeling software and computational hardware. Virtual screening can be performed on vast regions of chemical space while analyzing these structures with increased detail and accuracy. The concept of utilizing small molecules, in place of proteins, that exhibit biological activity towards a given protein target, whether activating or inhibiting, is known as non-peptide mimetics. These mimetics have several advantages over their peptide-based counterparts (decreased size, increased stability, increased lipophilicity etc.) while maintaining comparable or improved activities. Many of the properties used to characterize the oral bio-availability of drug candidates are also utilized in process design, which could allow for simultaneous optimization of several process and product variables on a property-based platform. This contribution outlines an algorithm for the design of mimetics based on information from existing pharmacophore models. Ideally, these techniques could be implemented alongside conventional high-throughput screening (HTS) efforts to alleviate the time and costs required to develop new therapeutic drugs with improved processing ability.