GSecretase Inhibitors

Several peptidic aldehydes have been reported to be inhibitors for either y-secretase or ¿S-secretase or both. Common to both series are lipophilic di- and tripeptides with bulky N-terminal protection, e.g. Z-LLL-CHO (MG132), Z-YIL-CHO, and Boc-GVV-CHO. The general lack of specificity of these aldehydes and their simultaneous inhibition of serine and cysteine proteases makes interpretation of data rather cumbersome. Indirect mechanisms through general protease inhibition result in complex concentration activity observations. Z-LLL-CHO (MG132), in fact, blocks maturation of the amyloid precursor protein. Some of these drawbacks were avoided by difluoro ketones as pioneered by Merryl Dow (Scheme 3.5.6), which

Val-Ile-OMe

Val-Ile-OMe

13 L-852,505
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