Unnatural or non-canonical amino acids expand the therapeutic potential of peptides but are often laborious to prepare in protected, coupling-ready form. We present a concise two-step synthesis from readily available terminal alkynes that combines mild gold(I) catalysis with inexpensive chiral tert-butylsulfinamide to deliver diverse, bench-stable building blocks—including N-methyl variants—with excellent enantiomeric excess. Preequipped with a removable N-sulfenyl protecting group and a mildly activated carboxyl, these amino acids couple directly without additional activation, proceeding with negligible to no epimerization even for challenging residues such as phenylglycine. The method integrates seamlessly into both solution- and solid-phase synthesis of peptides.

Today’s peptide therapeutics increasingly rely on chemistries beyond the 20 canonical amino acids to achieve exceptional pharmacological functions. Their manufacture relies on chemical methods, generating on average 13,000 kg of waste per kg of peptide, of which >50% is organic solvents. This talk will demonstrate how genetic code expansion enables the scalable biomanufacture of peptides and proteins that incorporate multiple non-canonical amino acids, in a reprogrammed E. coli host.

This presentation will highlight Immunethep’s strategy to advance a peptide-based vaccine concept targeting bacterial GAPDH (bGAPDH) to help prevent E. coli infection. We will review the target rationale and antigen design, including a tandem peptide construct built from selected bGAPDH-derived regions to target a conserved virulence factor while avoiding cross-reactivity with human GAPDH. We will summarize the development path, early learnings, and next steps toward a scalable, vaccine-ready profile.

Enzymatic macrocyclization offers a route to structurally complex peptides that are difficult to access through conventional methods. This presentation will describe recombinant production strategies that pair peptide expression with PapB-mediated thioether formation to generate conformationally constrained macrocycles and polymacrocycles. Key considerations include construct design, enzyme compatibility, reaction efficiency, product recovery, and analytical validation, with emphasis on enabling diverse peptide architectures for discovery and therapeutic development.

Parkinson’s disease still lacks therapies that neutralize pathogenic a-synuclein assemblies. HELICURE is a proprietary intranasal helical peptide platform designed to selectively engage toxic a-synuclein oligomers and fibrils while sparing the physiological monomer. In a mouse model of Parkinson’s disease with established synucleinopathy, our lead peptide reached dopaminergic neurons, reduced aggregated and phosphorylated a-synuclein across key disease-relevant brain regions, preserved nigrostriatal integrity, normalized neuroinflammation, and restored motor performance to near-normal levels.

The global market for peptide therapeutics is expanding rapidly, yet development is complicated by the inherent physicochemical instability and rapid clearance. This presentation discusses strategies to enable both oral and parenteral delivery of GLP-1 peptides through rigorous biophysical and molecular investigations. Using advanced techniques like NMR and SRS, three case studies from the drug substance, drug product, and delivery perspectives are explored. These studies elucidate the molecular mechanisms of liraglutide oligomerization, its aggregation from interfacial stress, and SNAC as an oral permeation enhancer, providing critical insights into overcoming key peptide stability and delivery obstacles.