[1S01e] 10. ASPIRE - Part 3

6:13 PM - 6:28 PM JST(9:13 AM - 9:28 AM UTC)

[1ASPR-24] Development of orthogonal phages from self-assembled non-linear peptides

○Kilian Colas¹ (1. Department of Chemistry, Graduate School of Science, The University of Tokyo (Japan))

Keywords:

self-assembly,peptides,mRNA display,artificial phages

Precision-engineering of artificial bacteriophages and viruses is of high interest for a multitude of applications, especially with the rise of antibiotic-resistant bacterial strains. A novel strategy to tackle this challenge is the use of self-assembling peptides. Libraries of fine-tuned, non-linear peptidic topologies are screened by the RaPID system to obtain potent binders to bacterial protein of interest. The resulting peptides can spontaneously self-assemble into phage- or capsid-like architectures that are bestowed specificity towards the chosen bacterial target. While precise inclusion of bespoke non-proteinogenic amino acids is crucial for successful self-assembly, multiple incorporations remain challenging for mRNA display screening system. We have successfully screened libraries of cyclic peptides with alternating L- an D-amino acids that adopt a "star-shaped" topology primed for self-assembly. Beyond their use as novel antibiotic modalities, these orthogonal phages have the potential to be further developed into an artificial phage-host system to explore genetic material delivery and replication.