title: The Immucillins: Design, Synthesis and Application of Transition- State Analogues.
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.
authors: Gary B
authors: GB
authors: Evans
authors: Vern L
authors: VL
authors: Schramm
authors: Ferrier Research Institute, Victoria University of Wellington, New Zealand. peter.tyler@vuw.ac.nz.
authors: Peter C
authors: PC
authors: Tyler
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives; D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase; D009699:N-Glycosyl Hydrolases; C019606:adenosylhomocysteine nucleosidase; D000225:Adenine; D000241:Adenosine; C517546:galidesivir