Protein engineering has provided us with a unique tool to construct perfectly defined peptide-based block copolymers with tunable characteristics. In our research we focus on two specific polypeptides: the capsid protein of cowpea chlorotic mottle virus (CCMV) and elastin-like polypeptides (ELP). ELPs display LCST behavior: at lower temperatures and salt concentrations the polypeptides adopt a random coil conformation and are water soluble; raising temperature and/or salt concentration leads to a reversible conformational change which is accompanied with an increase in hydrophobicity and aggregation. The transition temperature can be governed by the amino acid sequence. We have designed block copolymers of a hydrophobic and a more hydrophilic ELP which assembled into well-defined micelles. Upon fusion of nanobodies to the hydrophilic domain, the ELP micelles were able to target specific cell types that expressed the receptor for which the nanobody had affinity. By mixing in a modular fashion different ELP blocks with different function, targeted particles for photodynamic therapy were obtained.<br/>In a second line of investigation, we combined ELPs with the capsid protein of CCMV. This capsid is reversibly assembled and disassembled upon changes in pH: the capsid is formed at pH 5 and is disassembled at pH 7.5. Using the ELP fusion, this assembly behavior could also be controlled by changing temperature or salt concentration. Furthermore, by modifying the ELP sequence, CCMV capsids were obtained, which assembled in a stable manner under physiological conditions. This opens perspectives for using them in biomedical applications.

Well-defined stimulus-responsive polypeptide based assemblies

254th National Meeting (2017)

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