| 摘要 |
The present invention is directed to polypeptides and peptidomimetics that include a targeting moiety capable of transporting said polypeptide or peptidomimetic to the lysosome and/or across the blood brain barrier, and a lysosomal enzyme, methods for their production and precursors in their production. The polypeptides and peptidomimetics of the invention are produced using a method which utilizes a precursor comprising a tag. The reduces cleavage within the amino acid sequence of the polypeptide or peptidomimetic compared to levels of cleavage observed in the absence of the tag. These compounds are exemplified by IDS-Angiopep-2 polypeptides and peptidomimetics which can be used to treat MPS-I I. Where the targeting moiety transports the polypeptide or peptidomimetic across the blood brain barrier, these polypeptides and peptidomimetics can treat not only the peripheral disease symptoms, but may also be effective in treating CNS symptoms. Where the targeting moiety transports the polypeptide or peptidomimetic to the lysosomes, it is expected that the polypeptide or peptidomimetic will be more effective than IDS itself. |
