ubenimex

(redirected from Bestatin)

ubenimex

Alternative oncology
A competitive protease-inhibiting peptide isolated from the supernatant broth of cultured Streptomyces olivoreticuli that inhibits aminopeptidases B and N and leukotriene A4 hydrolase. Ubenimex stimulates the immune system, activates macrophages, increases production and secretion of IL-1 and IL-2, and stimulates T cells and haematopoiesis. It is in clinical trials for acute myeloid leukaemia and may be effective in treating various cancers, including Hodgkin lymphoma, leukaemia, melanoma, and cancers of the bladder, oesophagus, head and neck, lung and stomach.
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The samples were homogenized in a bullet blender with zirconium oxide beads in ice-cold buffer (in mmol [L.sup.-1]: Tris Base 100, Sucrose 500, NaF 200, NaCl 100, [Na.sub.4][O.sub.7][P.sub.2] 10, sodium orthovanadate 200, [beta]-glycerophosphate 300, with 5 mL/L Sigma protease inhibitor cocktail P8340 containing AEBSF 104, aprotinin 0.08, bestatin hydrochloride 4, E-64 1.4, leupeptin hemisulfate salt 2, pepstatin A 1.5) and protein concentrations were determined spectrophotometrically using Bradford protein assays (Bradford 1976).
Total protein from skin tissue was prepared by the addition 1:20 of T-PER Tissue Protein Extraction Reagent (PIERCE, Rockford, IL, USA) (25 mM bicine, 150 mM sodium chloride [pH 7.6]) containing protease inhibitors [100 mM 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride, 80 mM aprotinin, crystalline, 5 mM bestatin, 1.5 mM E-64, protease inhibitor, 2 M leupeptin, and 1 mM pepstatin A].
Frozen heart tissues (-80[degrees]C) of placebo- or Rapamycin-treated rats (n = 5 per group) were powdered under liquid nitrogen and lysed with ice cold lysis buffer (Cat#: AA-Lys, RayBiotech, Norcross, GA) supplemented with Okadaic Acid (0.1 [micro]M), sodium orthovanadate (250 [micro]M), sodium pyrophosphate (650 [micro]M), Bestatin (5 nM), and 1x cOmplete[TM] Protease Inhibitor Cocktail (Roche Life Sciences).
Briefly, cells were washed three times with ice-cold PBS and lysed in radioimmunoprecipitation assay (RIPA) lysis buffer (0.01mol/L sodium phosphate, pH7.2, 150 mmol/L NaCl, 2mmol/L EDTA, 1% NP-40, 1% sodium deoxycholate, 0.1% SDS, 2 mmol/L AEBSF, 130mmol/L bestatin, 14 mmol/L E64,0.3 mmol/L aprotinin, and 1 mmol/L leupeptin).
Obminska- Mrukowicz (2013).The effects of bestatin on humoral response to sheep erythrocytes in non- treated and cyclophosphamide- immunocompromised mice.ImmunopharmacolImmunotoxicol.
At the end of incubation the cells were washed with phosphate buffered saline and lysed with cell extraction buffer (10 mM Tris, pH 7.4, 100 mM NaCl, 1 mM EDTA, 1 mM EGTA, 1 mM NaF, 20 mM [Na.sub.4][P.sub.2][O.sub.7], 2 mM [Na.sub.3]V[O.sub.4], 1% Triton X-100, 10% glycerol, 0.1% SDS, 0.5% deoxycholate, 1 mM PMSF and protease inhibitor cocktail (2 mM [4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride], 14 [micro]M (N-(trans-epoxysuccinyl)-L-leucine 4-guanidinobutylamide], 130 [micro]M bestatin, 0.9 [micro]M leupeptin, 0.3 [micro]M aprotinin, and 1 mM EDTA)).
Effect of protease inhibitors on endogenous or exogenous [beta]-galactosidase in human fibroblasts Inhibitor Protease [beta]- [beta]- Galactosidase Galactosidase (endogenous) * (exogenous) ** None 100 100 E-64 Thiol 430 229 (Cysteine) *** Leupeptin Thiol 460 222 (Cysteine) *** Antipain Thiol 490 224 (Cysteine) *** Chymostatin Thiol 520 188 (Cysteine) *** Elastatinal Elastase 60 103 Pepstatin Pepsin 100 97 Phosphoramidon Metallopeptidase 110 88 Bestatin Aminopeptidase 110 90 * Relative enzyme activity in human fibroblasts with cathepsin A deficiency (galactosialidosis).
This mixture of protease inhibitors contains the serine protease inhibitors AEBSF (1 mmol [l.sup.-1]) and aprotinin (0.8 mmol [l.sup.-1]); the amino-peptidase inhibitor bestatin (50 [micro] mol [l.sup.-1]); the cysteine protease inhibitor E-64 (15 [micro] mmol [l.sup.-1]); the broad-spectrum protease inhibitor leupeptin (20 [micro] mmol [l.sup.-1]); and the aspartyl protease inhibitor pepstatin A (10 [micro] mmol [l.sup.-1]).
Isoserine derivatives constitute an essential fragment in natural products of high therapeutic value [3], such as Taxol (an anticancer agent), whose side chain is N-acyl-(2R,3S)-phenylisoserine; bestatin (a dipeptide modifier of the immune response), in which one of the amino acids is (2S,3R)-2-hydroxy-3-amino-3-phenylbutyric acid, and the kinostatins (potent inhibitors of the HIV-1 protease), in which one of the constituent amino acids is (2S,3S)-2-hydroxy-3-amino-3-phenylbutyric acid.
Wang et al., "Leukotriene [A.sub.4] hydrolase in rat and human esophageal adenocarcinomas and inhibitory effects of bestatin," Journal of the National Cancer Institute, vol.
The cells lysates were prepared using an ice-cold lysis buffer (50 mM Tris, 150 mM NaCl, 10 mM EDTA, 1% Triton) supplemented with a mixture of protease inhibitors containing antipain, bestatin, chymostatin, leupeptin, pepstatin, phosphoramidon, pefabloc, EDTA, and aprotinin (Boehringer, Mannheim, Germany).