TY - JOUR
T1 - Effect of Polymer Hydrophilicity and Molar Mass on the Properties of the Protein in Protein-Polymer Conjugates
T2 - The Case of PPEylated Myoglobin
AU - Pelosi, Chiara
AU - Duce, Celia
AU - Wurm, Frederik R.
AU - Tine, Maria R.
N1 - ACS deal
PY - 2021/5/10
Y1 - 2021/5/10
N2 - Polyphosphoesters (PPEs), a versatile class of biodegradable and biocompatible polymers, have been proposed as alternatives to poly(ethylene glycol) (PEG), which is suspected to be responsible for anaphylactic reactions in some patients after the administration of PEGylated compounds, e.g., in the current Covid-19 vaccines. We present the synthesis and characterization of a novel set of protein-polymer conjugates using the model protein myoglobin and a set of PPEs with different hydrophilicity and molar mass. We report an extensive evaluation of the (bio)physical properties of the protein within the conjugates, studying its conformation, residual activity, and thermal stability by complementary techniques (UV-vis spectroscopy, nano-differential scanning calorimetry, and fluorometry). The data underline the systematic influence of polymer hydrophilicity on protein properties. The more hydrophobic polymers destabilize the protein, the more hydrophilic PPEs protect against thermally induced aggregation and proteolytic degradation. This basic study aims at guiding the design of future PPEylated drugs and protein conjugates.
AB - Polyphosphoesters (PPEs), a versatile class of biodegradable and biocompatible polymers, have been proposed as alternatives to poly(ethylene glycol) (PEG), which is suspected to be responsible for anaphylactic reactions in some patients after the administration of PEGylated compounds, e.g., in the current Covid-19 vaccines. We present the synthesis and characterization of a novel set of protein-polymer conjugates using the model protein myoglobin and a set of PPEs with different hydrophilicity and molar mass. We report an extensive evaluation of the (bio)physical properties of the protein within the conjugates, studying its conformation, residual activity, and thermal stability by complementary techniques (UV-vis spectroscopy, nano-differential scanning calorimetry, and fluorometry). The data underline the systematic influence of polymer hydrophilicity on protein properties. The more hydrophobic polymers destabilize the protein, the more hydrophilic PPEs protect against thermally induced aggregation and proteolytic degradation. This basic study aims at guiding the design of future PPEylated drugs and protein conjugates.
KW - UT-Hybrid-D
UR - http://www.scopus.com/inward/record.url?scp=85104923699&partnerID=8YFLogxK
U2 - 10.1021/acs.biomac.1c00058
DO - 10.1021/acs.biomac.1c00058
M3 - Article
C2 - 33830737
AN - SCOPUS:85104923699
SN - 1525-7797
VL - 22
SP - 1932
EP - 1943
JO - Biomacromolecules
JF - Biomacromolecules
IS - 5
ER -