The inhibitory mechanism of wortmannine. (b) The structures of two series of designed proteasome inhibitors

March 11, 2024

• Title:       

   The inhibitory mechanism of wortmannine. (b) The structures of two series of designed proteasome inhibitors

• Image Source:

  Design and synthesis of a novel class of furan-based molecules as potential 20S proteasome inhibitors

• Mark:

  Figure 1

• Associated context:

  With the inspiration from the inhibition mechanism of wortmannine (Fig. 1a), a phosphatidylinositol-3 inhibitor, in which the acylfuran reacts with a nitrogen nucleophile by an addition-elimination process, producing a ring-opened Michael-adduct,²⁹ we choose the furanyl group as the C-terminal of our new proteasome inhibitors and dipeptide core structure I (Fig. 1b) as parent skeleton based  on the amino acid residuals in the active site of 20S proteasome. In addition, the statine structure II (Fig. 1b) can exhibit a good recognition between the inhibitor and proteasome.