methyl (2S)-5-carbamimidamido-2-(4-methylbenzenesulfonamido)pentanoate

• ChemBase ID: 73088
• Molecular Formular: C14H22N4O4S
• Molecular Mass: 342.41388
• Monoisotopic Mass: 342.1361762
• SMILES: c1c(ccc(c1)S(=O)(=O)N[C@H](C(=O)OC)CCCNC(=N)N)C
• Canonical SMILES: COC(=O)[C@@H](NS(=O)(=O)c1ccc(cc1)C)CCCNC(=N)N
• InChI: InChI=1S/C14H22N4O4S/c1-10-5-7-11(8-6-10)23(20,21)18-12(13(19)22-2)4-3-9-17-14(15)16/h5-8,12,18H,3-4,9H2,1-2H3,(H4,15,16,17)/t12-/m0/s1
• InChIKey: FKMJXALNHKIDOD-LBPRGKRZSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: methyl (2S)-5-carbamimidamido-2-(4-methylbenzenesulfonamido)pentanoate
• IUPAC Traditional name: methyl (2S)-5-carbamimidamido-2-(4-methylbenzenesulfonamido)pentanoate; TAME
• Synonyms: TAME; p-TOLUENESULFONYL-L-ARGININE METHYL ESTER HYDROCHLORIDE

Database IDs

• CAS Number: 901-47-3
• PubChem SID: 162038008
• PubChem CID: 1550286

CALCULATED PROPERTIES

• Acid pKa: 10.354648
• H Acceptors: 6
• H Donor: 4
• LogD (pH = 5.5): -1.8157995
• LogD (pH = 7.4): -1.7515968
• Log P: 0.23181371
• Molar Refractivity: 96.9272 cm^3
• Polarizability: 34.102673 Å^3
• Polar Surface Area: 134.37 Å^2
• Rotatable Bonds: 8
• Lipinski's Rule of Five: true

PROPERTIES

Physical Property

• Melting Point: 147°C

Safety Information

• Storage Condition: -20°C

Pharmacology Properties

• Target: APC

Product Information

• Salt Data: Free Base

DETAILS

MP Biomedicals - 05218728

MP Biomedicals Rare Chemical collection

Selleck Chemicals - S2225

Biological Activity

• Description: Tosyl-L-Arginine Methyl Ester (TAME) is an APC inhibitor.
• Targets: APC
• In Vitro: TAME inhibits cyclin proteolysis in mitotic Xenopus egg extract with IC50 of 12 μM. TAME at concentration of 1-200 μM arrests interphase extract treated with recombinant cyclin B1/Cdc2 complex in mitosis, with stable cyclin B1 and phosphorylated Cdc27. TAME at concentration of 200 μM dramaticly inhibits the ubiquitin ligase activity of the Anaphase-Promoting Complex (APC), accompanied by reduced binding of Cdh1 to APC. TAME addition to interphase extract reduces Cdc20 association with the APC in a dose-dependent manner partly by binding directly to APC, and the contribution motif is the C-terminal isoleucine-arginine (IR) tail on APC. ^[1] TAME is hydrolysed by trypsin with K_m of 0.328 mM. ^[2] TAME accelerates the ATP hydrolysis process about 12-fold. ^[3] TAME interacts with β and γ phosphate and the adenine ring of ATP by the guanidinium group and the aromatic ring. ^[4] TAME at concentration of 50 mM inhibits nutrient-induced germination and pressure-induced germination at 600 MPa in Bacillus subtilis. ^[5] TAME induces a concentration dependent contractile response on ileal strips with EC50 of 4.3 x 10^3 M. ^[6]

Protocol

• Protocol: Kinase Assay ^[1]
• 3H-TAME binding assay: ^3H-TAME (200 nM; 15 Ci/mmol) is added to 100 μl interphase Xenopus extract or HeLa cell lysate. APC is immunoprecipitated with Cdc27 antibody coupled to affiprep beads. The beads are washed with XB and radioactivity measured by scintillation counting. Alternatively, ^3H-TAME is added and Cdc27 immunoprecipitation is performed after one or two rounds of APC immunodepletion. Specific binding is calculated as the difference between counts associated with Cdc27 antibody beads compared to beads lacking antibody (mock IP)

References

• References: [1] Zeng X, et al. Cancer Cell, 2010, 18(4), 382-395.
• References: [2] Khantaphant S, et al. Food Chem, 2010, 120(3), 658-664.
• References: [3] Ma YQ, et al. J Inorg Organomet P, 2008, 18(4), 435-440.
• References: [4] Ma Y, et al. Dalton Trans, 2008, 28(8), 1081-1086.
• References: [5] Wuytack EY, et al. Appl Environ Microbiol, 2000, 66(1), 257-261.
• References: [6] Subratty AH, et al. Indian J Exp Biol, 1998, 36(6), 618-621.

REFERENCES

• Zeng X, et al. Cancer Cell, 2010, 18(4), 382-395.
• Khantaphant S, et al. Food Chem, 2010, 120(3), 658-664.
• Ma YQ, et al. J Inorg Organomet P, 2008, 18(4), 435-440.
• Ma Y, et al. Dalton Trans, 2008, 28(8), 1081-1086.
• Wuytack EY, et al. Appl Environ Microbiol, 2000, 66(1), 257-261.
• Subratty AH, et al. Indian J Exp Biol, 1998, 36(6), 618-621.