Taming the unnatural – innovative non-canonical amino acid synthesis for drug discovery and beyond Danielle Schultz Discovery Process Chemistry, MSD, USA Non-naturally occurring peptides are a growing therapeutic modality with most applications targeting endogenous proteins; however, advances in hit-to-lead platforms (such as mRNA display and DEL) have revealed that the druggable space of peptides can be greatly expanded. As a result, the discovery of peptide therapeutics is rapidly evolving and there is a growing need to dive into the non-canonical amino acid pool in order to fine tune biopharmaceutical properties such as potency, bioavailability and cell permeability. Through internal partnerships and academic-industrial collaborations, we have developed several methods to access non-canonical amino acids impacting both naturally occurring and synthetic peptides. A common thread throughout this work will be how sharing industrial challenges with our academic collaborators, coupled with our internal capabilities, can quickly transform ideas into innovative impacts.
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