Naturally occurring cyclic peptides have served as a valuable source of inspiration for the development of peptides that are useful in the detection and treatment of infectious diseases. Here, I will present the progress made in the development of two types of peptides: i) cyclic peptides for serological assays of SARS-CoV-2, and ii) potent antimicrobial peptides that exhibit remarkable activity against difficult-to-treat bacteria and biofilms.

The serological assay is based on the grafting of antigen epitopes into a stable cyclic peptide scaffold, which serves to enhance the stability and presentation of the peptides. Previously, we demonstrated the feasibility of this approach in targeting autoantibodies in rheumatoid arthritis (Gunasekera et al., 2018). Building upon this success, we have now applied the same concept to target antibodies against SARS-CoV-2. Specifically, we grafted selected epitopes into the sunflower trypsin inhibitory peptide 1 (SFTI-1) scaffold. One of the final peptides performed comparably to clinically used tests (Eriksson et al., 2023). Furthermore, we have expanded on this concept by ligation of oligonucleotide sequences to peptides, allowing for the development of a proximity extension assay.

Our design of cyclic antimicrobial peptides is based on an epitope (KR-12) derived from human cathelicidin LL-37. Here, we show that antimicrobial effect and stability can be improved through dimerization and cyclization of KR-12 (Gunasekera et al., 2020; Muhammad et al., 2023). The most promising example effectively eliminates Gram-negative bacteria (e.g. E. coli and MRSA), eradicates internalized bacteria without harming the infected cells, and prevents biofilm formation on catheters (White et al., 2022).

Eriksson C, et al., Chembiochem. Epub ahead of print: doi: 10.1002/cbic.202300103. (2023); Gunasekera S, et al., ACS Chem Biol.13:1525 (2018); Gunasekera S, et al., Front Microbiol, 11, 168 (2020); Muhammad T, et al., Biomedicines, 11, 504 (2023); White JK, et al., Cell Mol Life Sci, 79, 411 (2022)