Abstract:
:A big hurdle for the use of protein-based drugs is that they are easily degraded by proteases in the human body. In an attempt to solve this problem, we show the possibility to functionalize TM encapsulin nanoparticles with an mEETI-II knottin miniprotein from the cysteine-stabilized knot class. The resulting particles did not show aggregation and retained part of their protease inhibitive function. This imposes a protection toward protease, in this case, trypsin, degradation of the protein cage. The used chemistry is easy to apply and thus suitable to protect other protein systems from degradation. In addition, this proof of principle opens up the use of other knottins or cysteine-stabilized knots, which can be attached to protein cages to create a heterofunctionalized protein nanocage. This allows specific targeting and tumor suppression among other types of functionalization. Overall, this is a promising strategy to protect a protein of interest which brings oral administration of protein-based drugs one step closer.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Klem R,de Ruiter MV,Cornelissen JJLMdoi
10.1021/acs.molpharmaceut.8b00630subject
Has Abstractpub_date
2018-08-06 00:00:00pages
2991-2996issue
8eissn
1543-8384issn
1543-8392journal_volume
15pub_type
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