Browsing by Author "Garcia Quiroz, Felipe"

Despite decades of research since the discovery of the environmental sensitivity of tropoelastin, only a handful of elastin-inspired polypeptides departing from the canonical VPGXG motif, where X is any amino acid except proline, have been uncovered. Hence, the field of "smart" protein-polymers has evolved mainly through the introduction of innovative molecular architectures. Instead, we decided to explore sequence diversity as a necessary tool to broaden the biomedical and biotechnological utility of these "smart" protein-polymers. Using a new, highly parallel method for the synthesis of repetitive genes, we conducted a systematic study of the sequence constraints of the canonical VPGXG motif by substituting or inserting Alanine residues along this pentapeptide motif, which yielded new pentapeptide and hexapeptide, non-canonical ELP motifs. These studies led to the discovery of new families of hexapeptide motifs with fully reversible phase transition behavior and suggested an unexpected degree of sequence and conformational promiscuity in the canonical motif that hints at the existence a large space of amino acid sequences with intrinsic "smart" behavior. Moreover, this work shed light into the conformational requirements of the phase transition behavior and suggested the possibility to control the assembly of "smart" protein-polymers in a sequence-controlled manner.

"Smart" polymers that sense stimuli in aqueous environments and that respond with a pronounced change in their solvation are of great utility in biotechnology and medicine. Currently, however, only few peptide polymers are known to display this behavior. Here, we uncover the syntax -- defined as the arrangement of amino acids (letters) into repeat units (words) that have a functional behavior of interest -- of a novel and extensive family of genetically encoded "smart" peptide polymers, termed syntactomers, that dictates their ability to undergo a soluble to insoluble phase transition at temperatures above a lower critical solution temperature (LCST) or below an upper critical solution temperature (UCST). We show that this syntax ranges from phase transition polymers composed of simple repeats of a few amino acids to polymers whose syntax resembles the complex sequence of peptide drugs and protein domains that exhibit dual levels of function, as seen by their stimulus responsiveness and biological activity. This seamless fusion of materials and protein design embodied by syntactomers promises, we hope, a new generation of designer polymers with multiple levels of embedded functionality that should lead to new functional materials of broad interest