Chemists make better mimetic mucins

Mucus is slippery, slimy, and full of glycosylated proteins that can disarm pathogens. To study the properties of these proteins, which are called mucins, chemists can create synthetic versions of these mucus polymers. Many researchers have focused on the chemical groups that stick out from the polymers’ long molecular chains, but few groups have studied the backbone itself. Katharina Ribbeck’s and Laura Kiessling’s groups at the Massachusetts Institute of Technology have been working together to do that by using simplified synthetic versions of mucins (ACS Cent. Sci. 2021, DOI: 10.1021/acscentsci.0c01569). They found that the extension of the backbone is essential to molecular function. It makes the polymers more soluble and less likely to aggregate. Kiessling says that, counterintuitively, the polymers her group made with cis bonds extend longer than those with trans bonds. That lengthening occurs because of allylic strain and hydrophobic effects. The researchers compared the synthetic mucins with natural ones and found the cis-bond-containing polymers with extended backbones not only look like natural ones under an atomic force microscope but also bind a toxin released by Vibrio cholerae just like natural mucins do. “We think of mucus as a yuck, but it does a lot of great things for us,” Kiessling says. She hopes tunable mimics can become powerful tools for mucin research and improving health.