Discovery of AICAR Tfase inhibitors that disrupt requisite enzyme dimerization

Isomeric Control of Protein Recognition with Amino Acid‐ and Dipeptide‐Functionalized Gold Nanoparticles

“…Protein-surface recognition features prominently in applications in broad fields of science and technology, such as control of cellular processes, [1,2] construction of biological sensors, [3] and creation of hybrid materials. [4] To date, various strategies to target protein-protein interactions have been proposed.…”

Small-Molecule Inhibition of TNF-α

“…demonstrates that small molecules that function by disrupting tightly preassociated oligomeric proteins are feasible. Although small-molecule inhibitors that block dimer formation exist for a number of intracellular homodimeric proteins (10,17), many may function through a predissociation-dependent mechanism. For example, an inhibitor (18,19) of inducible nitrous oxide synthase (iNOS) inhibits the intracellular association of iNOS monomers into enzymatically active iNOS dimer yet is inactive against isolated dimeric iNOS.…”

Fluorescence Observables and Enzyme Kinetics in the Investigation of PPI Modulation by Small Molecules: Detection, Mechanistic Insight, and Functional Consequences

“…Dissociative inhibition seems to be a useful strategy also versus two other HIV-1 enzymes, reverse transcriptase and IN [97]. Among the fewer examples concerning other dimeric enzymes, we mention the inhibition of dimeric aminoimidazole carboxamide ribonucleotide transformylase (AICAR Tfase) by a small compound, Cappsin 1 [98], and that of 3C-like proteinase of severe acute respiratory syndrome coronavirus by some octapeptides derived from the protein N-terminal [99]. Apparently, no available examples involve more-than-dimeric enzymes, and the dissociative inhibition model has not been extended to higher oligomers than dimers.…”