Self-assembly of temperature-responsive di-block polypeptides functionalized with unnatural amino acids

Rotem Azulay, Daniela S. Strugach, Miriam Amiram

Research output: Contribution to journalArticlepeer-review


The incorporation of unnatural amino acids (uAAs) into protein-based polymers has emerged as a powerful methodology to expand their chemical repertoire. Recently, we demonstrated that incorporating uAAs into two temperature-responsive protein-based polymers—namely resilin- and elastin-like polypeptides (RLPs and ELPs, respectively)—can alter their properties. In this study, we incorporated aromatic uAAs into the protein sequence of RLP–ELP diblocks to yield new and diverse assemblies from a single DNA template. Specifically, we show that incorporating aromatic uAAs can modulate the phase-transition behaviors and self-assembly of the diblocks into various morphologies, including spherical and cylindrical micelles and single- and double-layered vesicles, with some constructs also demonstrating a temperature-responsive shape-shifting behavior. Next, we evaluated the ability of the RLP–ELP assemblies to encapsulate a chemotherapeutic drug, doxorubicin, and show how the identity of the incorporated uAAs and the morphology of the nanostructure affect the encapsulation efficiency. Taken together, our findings demonstrate that the multi-site incorporation of uAAs into temperature-responsive, amphiphilic protein-based diblock copolymers is a promising approach for the functionalization and tuning of self-assembled nanostructures.

Original languageEnglish
Article numbere4878
JournalProtein Science
Issue number2
StatePublished - 1 Feb 2024


  • elastin-like polypeptides
  • genetic code expansion
  • resilin-like polypeptides
  • self-assembly
  • unnatural amino acids

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry


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