“Smart” polymers that respond to stimuli in their aqueous environments with a pronounced physical change are of great utility in biotechnology and medicine. Currently, however, only few peptide polymers show this behavior. In this project, we seek to uncover the relationship between the syntax of peptide polymers and their lower critical solution temperature (LCST) transition behavior as well as a class of peptide polymers that show the reverse –upper critical solution temperature (UCST)– behavior. We have found that the syntax of these functional peptide polymers ranges from polymers composed of simple repeats of a few amino acids to those whose syntax resembles the complex non-repetitive syntax of protein domains, and that the concept of syntax can be deployed to re-program bioactive peptides to exhibit dual functions, as seen by their stimulus responsiveness and biological activity. The unique linguistic features exhibited by these peptide polymers suggests that peptide polymers can be best described as linear macromolecules that are composed of amino acid “letters” that are organized as “words”, with higher order organization of one or more words that repeat or recur to create a “phrase” (the macromolecule) and postulate that the syntax –word order– of this class of polymers controls their function. Hence, by analogy to syntax in natural language —defined as the arrangement of words in a phrase that controls its meaning, we suggest that peptide polymers are better described as syntactomers – polymers whose properties are controlled by their organization as a collection of letters into words and the higher order organization of words into functional phrases.
Syntactomers: Exploring the Nexus between Syntax and Polymer Design
Publications
Advances in Understanding Stimulus Responsive Phase Behavior of Intrinsically Disordered Protein Polymers. K.M. Ruff; S. Roberts; A. Chilkoti; R.V. Pappu. (2018).
Convergence of Artificial Protein Polymers and Intrinsically Disordered Proteins. M. Dzuricky; S. Roberts; A. Chilkoti. (2018).
Sequence directionality dramatically affects LCST behavior of elastin-like polypeptides. N.K. Li; S. Roberts; F.G. Quiroz; A. Chilkoti; Y.G. Yingling. (2018).
Combinatorial codon scrambling enables scalable gene synthesis and amplification of repetitive proteins. N.C. Tang; A. Chilkoti. (2016).
Sequence heuristics to encode phase behaviour in intrinsically disordered protein polymers. F.G. Quiroz; A. Chilkoti. (2015).
Elastin-like polypeptides as models of intrinsically disordered proteins. S. Roberts; M. Dzuricky; A. Chilkoti. (2015).
Molecular description of the LCST behavior of an elastin-like polypeptide. N.K. Li; F. García Quiroz; C.K. Hall; A. Chilkoti; Y.G. Yingling. (2014).
A unified model for de novo design of elastin-like polypeptides with tunable inverse transition temperatures. J.R. McDaniel; C.D. Radford; A. Chilkoti. (2013).
A highly parallel method for synthesizing DNA repeats enables the discovery of ‘smart’ protein polymers. M. Amiram; F. García Quiroz; D.J. Callahan; A. Chilkoti. (2011).