Synthesis and Site-selective Modification of Amino Acids and Peptides
Due to their high potency and target selectivity, the use of peptides as potential drug candidates has become a prominent new modality in contemporary drug discovery. However, widespread adoption of peptidomimetic drugs as viable pharmaceutical candidates is often hampered by their poor membrane permeability and biological instability, preventing oral administration and often leading to poor pharmacokinetic properties. Synthetic chemistry has shown great promise to help to tune these properties by overcoming the inherent limitations shown by biologically driven modifications, e.g. by accessing molecules that are difficult or impossible to obtain via gene expression systems, through the introduction of unnatural amino acids (UAAs) or by affecting peptide conformation through macrocyclisations. However, the application of such strategies remains limited by the lack of general and readily streamlined synthetic capabilities. To tackle this issue, our group exploits radical chemistry to develop general approaches to access libraries of chiral, non-canonical amino acids from sustainable feedstocks, and to selectively modify AA residues in complex peptides.
Selected publications
4. Accessing α-Amino Ketyl Radicals from β-Amino Alcohols via Chemoselective Hydrogen Atom Transfer Catalysis; K. Merkens, N. Sanosa, I. Funes-Ardoiz, A. Gómez-Suárez* ACS Catal. 2022, 12, 13186–13192
3. Synthesis of γ-Oxo-α-amino Acids via Radical Acylation with Carboxylic Acids K. Merkens,† F.J. Aguilar Troyano,† K. Anwar, A. Gómez-Suárez* J. Org. Chem. 2021, 12, 8448–8456 (†These authors contributed equall) Synfacts Highlight OPR&D – Highlights from the literature
2. Radical‐Based Synthesis and Modification of Amino Acids; F.J. Aguilar Troyano,† K. Merkens,† K. Anwar, A. Gómez-Suárez* Angew. Chem. Int. Ed. 2021, 60, 1098-1115. (†These authors contributed equally)
1. Synthesis of Unnatural alpha-Amino Acid Derivatives via Light-mediated Radical Decarboxylative Processes; K. Merkens,† F.J. Aguilar Troyano,† J. Djossou, A. Gómez-Suárez* Adv. Synth. Catal. 2020, 362, 2354-2359 (†These authors contributed equally) Synfact Highlight OPR&D – Highlights from the literature
