A NEW THERAPEUTIC MODALITY FOR DIAGNOSING AND TREATING DISEASE
Peptides are modular chains of amino acids that serve as natural ligands for many receptors in the body and offer attractive attributes for new drug discovery. The ability to create large peptide diversity libraries offers the potential to develop novel therapeutics with high target affinity and specificity. However, low in vivo stability and poor pharmacokinetics have greatly limited the application of peptides in pharmaceutical development. Lassogen aims to change this paradigm through a new class of remarkable peptides uncovered in nature.
Gifts from nature. Lasso peptides are naturally produced by bacteria and possess a distinctive threaded lariat fold that offers a 3D array of functionality for engaging biological targets. This unique lasso structure engenders these systems with beneficial properties such as high stability (to proteases, low pH, and heat) and potent biological activities. Our new genome mining algorithms have been trained using machine learning and indicate that millions of diverse lasso peptides are likely to reside in nature - a veritable untapped goldmine of new activities and novel mechanisms of action for drug discovery and development.
Linear peptides are strings of amino acids that are easily degraded in vivo
Bacteria convert linear peptides into highly stable, bioactive lasso peptides
Millions in nature
Unique 3D structure
Infinite lasso diversity
Ideal size and shape for receptor binding
Diverse lasso structures have translated into a wide range of mechanisms of action, including activity vs challenging G protein-coupled receptors (GPCRs). Many therapeutic applications of lasso peptides can be envisioned.
Lassogen’s cutting-edge platform integrates genomics, advanced synthetic biology, and AI-data analytics to enable accelerated discovery, optimization, and production of our novel lasso peptide-based therapeutics. Our AI-driven algorithms mine genomic space and predict lasso biosynthesis pathway genes. Cell-free biology rapidly converts lasso sequence data into molecules that can be screened. Hits are optimized through lasso evolution methods. Lassos of interest are scaled for development through engineered fermentation strains.
Hegemann, J.D., et al., Lasso Peptides: An Intriguing Class of Bacterial Natural Products, Acc. Chem. Res., 2015, 48, 1909−1919. doi: 10.1021/acs.accounts.5b00156
Tietz, J.I., et al., A new genome-mining tool redefines the lasso peptide biosynthetic landscape, Nature Chem Bio, 2017, 13, 470-478. doi: 10.1038/nchembio.2319
DiCaprio, A.J., et al., Enzymatic Reconstitution and Biosynthetic Investigation of the Lasso Peptide Fusilassin, J. Am. Chem. Soc., 2019, 141, 290−297. doi: 10.1021/jacs.8b09928
Al Toma, R.S., et al., Site-Directed and Global Incorporation of Orthogonal and Isostructural Noncanonical Amino Acids into the Ribosomal Lasso Peptide Capistruin, ChemBioChem, 2015, 16, 503 – 509. doi: 10.1002/cbic.201402558