Catalytically active recombinant memapsin and methods of use thereof

摘要: Methods for the production of purified, catalytically active, recombinant memapsin (2) have been developed. The substrate and subsite specificity active enzyme determined. information was used to design analogs natural that can inhibit function (2). are based on peptide sequences, shown be related substrates contain at least one analog an amide bond which is not capable being cleaved by Processes synthesis two analogues including isosteres sites critical amino acid residues were developed analogues, OMR99-1 OM99-2, synthesized. OM99-2 octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with Leu-Ala substituted a transition-state isostere hydroxyethylene group (Fig. 1). inhibition constant 1.6 x 109 M against pro-memapsin 2. Crystallography 2 bound this inhibitor determine three dimensional structure protein, as well importance various in binding. This those skilled art new inhibitors, using commercially available software programs techniques familiar organic chemistry enzymology, inhibitors (2), useful diagnostics treatment and/or prevention Alzheimer's disease.