Modulation of proteasome subunit selectivity of syringolins.

Development of selective or dual proteasome subunit inhibitors based on syringolin B as a scaffold is described. We focused our efforts on a structure-activity relationship study of inhibitors with various substituents at the 3-position of the macrolactam moiety of syringolin B analogue to evaluate whether this would be sufficient to confer subunit selectivity by using sets of analogues with hydrophobic, basic and acidic substituents, which were designed to target Met45, Glu53 and Arg45 embedded in the S1 subsite, respectively. The structure-activity relationship study using systematic analogues provided insight into the origin of the subunit-selective inhibitory activity.

Synthesis and biological evaluation of echinomycin analogues as potential colon cancer agent.

Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death, thus a novel chemotherapeutic agent for colon cancer therapy is needed. In this study, analogues of echinomycin, a cyclic peptide natural product with potent toxicity to several human cancer cell lines, were synthesized, and their biological activities against human colon cancer cells were investigated. Analogue 3 as well as 1 inhibit HIF-1α-mediated transcription.

Solid-Phase Total Synthesis of Sandramycin and Its Analogues.

Solid-phase total synthesis of sandramycin (), which is a -symmetric cyclic decadepsipeptide natural product, and its analogues is described. On-resin ester formation and [5+5] peptide coupling allowed the preparation of a range of desymmetrized analogues. An amino acid residue that would not hamper the biological activity of was successfully identified, and probe molecules and dimeric analogues were prepared on the basis of the result of the structure-activity relationship study.