Uses
HMB-Val-Ser-Leu-VE is a prototype vinyl ester inhibitor. HMB-Val-Ser-Leu-VE is against trypsin-like (T-L) proteasome activity with an IC50 of 0.033 μM[1].
Definition
ChEBI: N-(3-hydroxy-2-methylbenzoyl)-l-valyl-n-[(1s,2e)-4-ethoxy-1-(2-methylpropyl)-4-oxo-2-butenyl]-l-serinamide is a dipeptide.
Biological Activity
hmb-val-ser-leu-ve is an irreversible, cell-permeable, potent and specific inhibitor of the trypsin-like activity of the 20s proteasome with ic50 value of 33 nm [1].the 20s proteasome is a 700 kda, cylinder-shaped protease with multiple catalytic centers within the ubiquitin-proteasome pathway and plays an important role in the selective degradation of intracellular proteins. proteasomes remove abnormal proteins and play an important role in cell-cycle progression and apoptosis [1][2].hmb-val-ser-leu-ve is a tripeptide-based compound bearing a c-terminal vinyl ester that acts as a potent and selective inhibitor of the trypsin-like activity of the 20s proteasome with ic50 value of 33 nm [1]. in two colon-carcinoma cell lines (coo115, hct116), hmb-val-ser-leu-ve was nontoxic and did not affect cell proliferation. in hla-a2 positive lymphoblastoid cells, hmb-val-ser-leu-ve caused a dose-dependent increase of clg-specific killing, suggesting that hmb-val-ser-leu-ve favored the generation and presentation of immunogenic peptides presented by mhc class i molecules [1].
References
[1]. marastoni m, baldisserotto a, cellini s, et al. peptidyl vinyl ester derivatives: new class of selective inhibitors of proteasome trypsin-like activity. j med chem. 2005 jul 28;48(15):5038-42.
[2]. demartino gn, slaughter ca. the proteasome, a novel protease regulated by multiple mechanisms.
