PE Lab - Research

A single atom substitution (O to S) in the amide bond results in the formation of a thioamide. Although an isostere, the physico-chemical properties of a thioamide is quite distinct from an amide. The restricted C-N bond rotation and larger size of the sulfur results in unique conformational properties of the thioamide containing polypeptide. We have also revealed that a thioamide is heavily desolvated, which makes these peptides more hydrophobic than their oxo-counterpart. We incoporate thioamide into model cyclic peptides, hormones and mini-proteins to alter their shapes, properties and biological activity.

Although frequently found in naturally occurring peptides, N-methylation is rare in proteins. The N-methyl group heavily restricts the torsion about the amide bond and at the same time reduces the rotational barrier about the C-N bond. This dual feature sometimes lead to unpredictable conformational properties of N-methylated polypeptides. However, when carefully tuned, N-methylation can enforce a heavily restricted conformational space that might be desirable towards the design of bioactive peptides. We engineer N-methyl groups into naturally occurring Antimicrobial Peptides (AMPs) to combat the rising antimicrobial resistance against antibiotics.