77443-49-3Relevant articles and documents
Design, synthesis and biological evaluation of dipeptides as novel non-covalent 20S proteasome inhibitors
Yang, Ya-Jun,Wang, Ke,Yang, Ying,Lai, Fang-Fang,Chen, Xiao-Guang,Xiao, Zhi-Yan
, p. 436 - 451 (2021/04/22)
Based on the interaction modes of the natural 20S proteasome inhibitors TMC-95A, we have previously discovered a dipeptide 1. To explore the SAR around compound 1, we designed and synthesized a series of dipeptides (8–38) with a fragment-based strategy. Among them, nine compounds showed significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome with IC50 values at the submicromolar level, which were comparable or even superior to the parent compound 1. Meanwhile, they displayed no significant inhibition against trypsin-like and caspase-like activities of 20S proteasome. The results suggested the feasibility to design dipeptides as novel and potent 20S proteasome inhibitors. (Figure presented.).
Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors
Niroula, Doleshwar,Hallada, Liam P.,Le Chapelain, Camille,Ganegamage, Susantha K.,Dotson, Devon,Rogelj, Snezna,Groll, Michael,Tello-Aburto, Rodolfo
, p. 962 - 977 (2018/09/04)
The peptidic β-lactone proteasome inhibitors (PIs) cystargolides A and B were used to conduct structure-activity relationship (SAR) studies in order to assess their anticancer potential. A total of 24 different analogs were designed, synthesized and evaluated for proteasome inhibition, for cytotoxicity towards several cancer cell lines, and for their ability to enter intact cells. X-ray crystallographic analysis and subunit selectivity was used to determine the specific subunit binding associated with the structural modification of the β-lactone (P1), peptidic core, (Px and Py), and end-cap (Pz) of our scaffold. The cystargolide derivative 5k, structurally unique at both Py and P1, exhibited the most promising inhibitory activity for the β5 subunit of human proteasomes (IC50 = 3.1 nM) and significant cytotoxicity towards MCF-7 (IC50 = 416 nM), MDA-MB-231 (IC50 = 74 nM) and RPMI 8226 (IC50 = 41 nM) cancer cell lines. Cellular infiltration assays revealed that minor structural modifications have significant effects on the ability of our PIs to inhibit intracellular proteasomes, and we identified 5k as a promising candidate for continued therapeutic studies. Our novel drug lead 5k is a more potent proteasome inhibitor than carfilzomib with mid-to-low nanomolar IC50 measurements and it is cytotoxic against multiple cancer cell lines at levels approaching those of carfilzomib.
Development of supramolecular organo-gel based on tripeptide skeletons
Azuma, Eriko,Kuramochi, Kouji,Tsubaki, Kazunori
body text, p. 680 - 684 (2010/07/15)
Boc-Ser-Val-Gly-OCH2Ph (31) showed high gelation abilities in the aromatic solvents, particularly in toluene. The minimum gelation concentration of 31 in toluene was 10 mg/ml, suggesting that 2500 molecules of toluene were immobilized by each m
