AI Article Synopsis
- A polymeric nanogel was developed to sequester and inactivate the lysosomal enzyme, acid α-glucosidase (GAA), using a pH-sensitive β-thiopropionate cross-linker.
- When the pH is lowered to 5.0, about 75% of the enzyme's activity is restored due to the breakdown of the cross-linker, leading to the swelling and release of the enzyme from the nanogel.
- This approach of controlling protein activity through pH changes could offer new therapeutic strategies for treating lysosomal storage diseases.
Article Abstract
A polymeric nanogel has been used to sequester and turn off a lysosomal protein, acid α-glucosidase (GAA). The nanogel contains a β-thiopropionate cross-linker, which endows the nanogel with pH-sensitivity. While encapsulation of the enzyme fully turns off its activity, approximately 75% of the activity is recovered upon reducing the pH to 5.0. The recovered activity is ascribed to pH-induced degradation of the β-thiopropionate cross-linker causing the swelling of the nanogel and ultimately causing the release of the enzyme. We envision that strategies for sequestering protein molecules and releasing them at lysosomal pH might open up new directions for therapeutic treatment of lysosomal storage diseases.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229022 | PMC |
| http://dx.doi.org/10.1021/bm501091p | DOI Listing |
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