“Often described as ‘Goldilocks drugs,’ macrocyclic peptides are smaller than biologics like antibodies but larger than small molecules. With their just-right size, macrocyclic peptides can travel into spaces too small for biologics to reach and, thanks to their structural rings of amino acids, can target protein-protein interactions that evade small molecules.

Researchers at the biopharmaceutical company Merck have taken advantage of macrocyclic peptides’ unique properties to develop enlicitide decanoate (enlicitide), an oral macrocyclic peptide drug that lowers ‘bad’ cholesterol by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9)…

The only problem is that enlicitide is a very complicated drug to make. ‘This is a monster of a molecule,’ said Alison Narayan, a chemist focused on biocatalysis at the University of Michigan.

Recently, researchers at Merck developed a vastly more efficient and sustainable way of synthesizing enlicitide using engineered enzymes to catalyze different reaction steps, a process called biocatalysis. The new method reduced the number of synthesis steps by more than half and led to a 39 percent yield of the molecule on a multi-kilogram-scale. The team published their findings in Science.

From The Scientist.