TY - JOUR
T1 - Protecting Encapsulin Nanoparticles with Cysteine-Knot Miniproteins
AU - Klem, Robin
AU - De Ruiter, Mark V.
AU - Cornelissen, Jeroen J.L.M.
N1 - ACS deal
PY - 2018/8/6
Y1 - 2018/8/6
N2 - 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.
AB - 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.
KW - UT-Hybrid-D
KW - bacterial nanocompartment
KW - nanocage
KW - protease inhibitor
KW - antibody substitute
UR - http://www.scopus.com/inward/record.url?scp=85051225063&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.8b00630
DO - 10.1021/acs.molpharmaceut.8b00630
M3 - Article
AN - SCOPUS:85051225063
VL - 15
SP - 2991
EP - 2996
JO - Molecular pharmaceutics
JF - Molecular pharmaceutics
SN - 1543-8384
IS - 8
ER -