INSOLUTION OM99-2 - CAS 314266-76-7 - CALBIOCHEM

General description

A peptidomimetic, highly potent, tight-binding transition-state analog inhibitor of human brain β-secretase (K_i = 1.6 nM, recombinant memapsin-2; K_i = 9.58 nM, recombinant pro-memapsin 2). Designed from the template of the β-secretase site of Swedish β-amyloid precursor protein (APP) with Asp to Ala replacement. Includes a nonhydrolyzable hydroxyethylene isostere between Leu and Ala. Also reported to inhibit cathepsin D at higher levels (K_i = 48 nM).

An eight residue peptidomimetic, tight binding transition-state analog inhibitor of human brain memapsin 2 (K_i = 1.6 nM, recombinant memapsin 2; K_i = 9.58 nM, recombinant pro-memapsin 2). Also inhibits cathepsin D (K_i = 48 nM). This aspartyl protease inhibitor is designed from the template of the β-secretase site of Swedish β-amyloid precursor protein (APP) with Asp to Ala replacement; also includes a nonhydrolyzable hydroxyethylene isostere between Leu and Ala.

Biochem/physiol Actions

Cell permeable: no

Primary Target
human brain memapsin 2

Product does not compete with ATP.

Reversible: no

Target K_i: 1.6 nM against recombinant memapsin 2; 9.58 nM against recombinant pro-memapsin 2; 48 nM against cathepsin D

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Sequence

Glu-Val-Asn-Leu-Ψ-Ala-Ala-Glu-Phe [Ψ denotes replacement of CONH by (S)-CH(OH)CH₂]

Physical form

A 1 mM (250µg in 280 µl) solution in DMSO. Supplied as a trifluoroacetate salt.

Reconstitution

Following initial thaw, aliquot and freeze (-20°C). Avoid freeze/thaw cycles of solutions.

Other Notes

Ghosh, A.K., et al. 2001. J. Med. Chem.44, 2865.
Turner III, R.T., et al. 2001. Biochemistry40, 10001.
Ghosh, A.K., et al. 2000. J. Am. Chem. Soc.122, 3522.
Hong, L., et al. 2000. Science290,150.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Molecular Weight: 892.99. Empirical Formula: C₄₁H₆₄N₈O₁₄. Quality Level: 100. Assay: ≥. 90% (HPLC). form: liquid. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, desiccated, protect from light. shipped in: ambient. storage temp.: −. 20°C. InChI: 1S/C39H60N8O14/c1-18(2)12-24(43-36(57)25(16-29(41)49)45-38(59)32(19(3)4)47-35(56)23(40)15-30(50)51)28(48)13-20(5)33(54)42-21(6)34(55)44-26(17-31(52)53)37(58)46-27(39(60)61)14-22-10-8-7-9-11-22/h7-11,18-21,23-28,32,48H,12-17,40H2,1-6H3,(H2,41,49)(H,42,54)(H,43,57)(H,44,55)(H,45,59)(H,46,58)(H,47,56)(H,50,51)(H,52,53)(H,60,61)/t20-,21+,23+,24+,25+,26+,27+,28+,32+/m1/s1. InChI key: JCNFYXCBSRPSLY-QYTLZHMISA-N. Storage Class Code: 10 - Combustible liquids. WGK: WGK 1. Flash Point(F): 188.6 °F - (Dimethylsulfoxide). Flash Point(C): 87 °C - (Dimethylsulfoxide).