The Immucillins: Design, Synthesis and Application of Transition- State Analogues

Title:The Immucillins: Design, Synthesis and Application of Transition- State Analogues

Volume: 22 Issue: 34

Author(s): Gary B. Evans, Vern L. Schramm and Peter C. Tyler

Affiliation:

Keywords: Deaminases, Iminoribitols, N-ribosyltransferases, nucleoside analogues, transition-state analogues, transition-state theory.

Abstract: Transition-state analysis based on kinetic isotope effects and computational chemistry provides electrostatic potential maps to serve as blueprints for the design and chemical synthesis of transition-state analogues. The utility of these molecules is exemplified by potential clinical applications toward leukemia, autoimmune disorders, gout, solid tumors, bacterial quorum sensing and bacterial antibiotics. In some cases, transition-state analogues have chemical features that have allowed them to be repurposed for new indications, including potential antiviral use. Three compounds from this family have entered clinical trials. The transition-state analogues bind to their target proteins with high affinity and specificity. The physical and structural properties of binding teach valuable and often surprising lessons about the nature of tight-binding inhibitors.

Cite this article as:

Evans B. Gary, Schramm L. Vern and Tyler C. Peter, The Immucillins: Design, Synthesis and Application of Transition- State Analogues, Current Medicinal Chemistry 2015; 22 (34) . https://dx.doi.org/10.2174/0929867322666150821100851