This research is led by Timothy J. Deming (Department of Chemistry and Biochemistry and Department of Bioengineering, University of California, Los Angeles, United States).
There is considerable interest in understanding the formation of protein coacervates in living systems, including both their biological functions as well as how their physical properties correlate with molecular features of the proteins. While considerable advances have been made in correlating protein or peptide sequences with coacervation propensity, there remains a need for well-defined model systems that are also able to replicate the many functional features of coacervate forming proteins. These include being able to respond to physiologically relevant stimuli including changes in pH, counterions, temperature, and exposure to oxidizing and reducing agents. Further, for potential downstream use in applications such as therapeutic delivery and materials science it is important that coacervate properties can be readily and predictably tuned by adjustment of molecular features.
Recently, the authors reported the synthesis and coacervation properties of the homopolypeptides 1a−d as shown in Figure. A variety of features in these polypeptides allow them to form coacervates in water that can respond to changes in physiologically relevant stimuli, similar to natural protein based coacervates. Coacervation can also be switched off and on via addition of mild oxidizing and reducing reagents, respectively. These properties are enabled by multifunctional side-chains present in every repeating unit, which contain molecular elements that are sensitive to changes in the solution environment. Unlike natural proteins that rely on complex sequences of different amino acid residues for such multifunctionality, these sequentially uniform homopolypeptides possess multiple, precisely controlled functional side-chain features that allow for a more straightforward investigation and understanding of structure-property relationships. In order to better understand how side-chain molecular features in 1a−d affect coacervate formation and to learn how coacervate properties can be altered for different uses, they have prepared side-chain modified variants of these parent homopolypeptides. their efforts focused on precise modification of three different regions of the side-chains: the amino acid core (2b), the linker (3c), and the terminal charged group (4a−d, Figure). These modifications were chosen to investigate effects of altered side-chain lengths and hydrophobicity (2b, 3c), as well as to compare how charge reversal in anionic 4a−d affects coacervation properties compared to those of cationic 1a−d. Their synthetic method is advantageous for preparation of a variety of different multifunctional homopolypeptides due to the efficiency of the post-polymerization modifications as well as the modular nature of the synthesis, which allows facile substitution of small molecule components to generate diversity.
See the article:
Influence of Side-Chain Molecular Features on Aqueous Coacervation of Multifunctional Homopolypeptides
https://doi.org/10.1021/polymscitech.4c00003
