Beschreibung:
<jats:p>Cathepsin D is a lysosomal aspartic proteinase that has been implicated in several pathological processes such as breast cancer and Alzheimer's disease. We designed and synthesized a number of quenched fluorogenic substrates with P2 variations in the series AcEE(EDANS)KPIXFFRLGK(DABCYL)E‐NH<jats:sub>2</jats:sub>, where X=cysteine, methylcysteine, ethylcysteine, <jats:italic>tert</jats:italic>‐butylcysteine, carboxymethylcysteine, methionine, valine or isoleucine. Most of the fluorogenic substrates exhibited greater <jats:italic>k</jats:italic>
<jats:sub>cat</jats:sub>/<jats:italic>K</jats:italic>
<jats:sub>m</jats:sub> ratios than the best cathepsin D substrates described so far. Differences in kinetic constants, which were rationalized using structure‐based modeling, might make certain substrates useful for particular applications, such as active site titrations or initial velocity determination using a fluorescent plate reader.</jats:p>