Collagen, the most abundant protein in mammals, is a key contributor to the strength and stability of skin, bones, and connective tissue. Collagen formation is thus vital for the integrity of skin, tendons, and the tissue in essentially any organ. Excessive collagen formation is, however, characteristic of fibrotic and malignant diseases, which include major global health issues.

The Wennemers group has used collagen model peptides, CMPs, to understand the stability of collagen at the molecular level and to establish functional synthetic collagen triple helices.^{1, 2} These include pH-responsive synthetic collagen,³ hyperstable triple helices,⁴ and heterotrimeric collagen.⁵ Building on these data, we designed and synthetized a chemical probe for the simultaneous monitoring and targeting of lysyl oxidase LOX-mediated collagen cross-linking.⁶ The probe allows for the detection of LOX activity in vivo and in tissue sections.

References

1. H. Wennemers. Peptides – Molecular Allrounders. Chimia. 2021, 75, 6, 525

2a. T. Fiala, E. P. Barros, M.-O. Ebert, E. Ruijsenaars, S. Riniker, and H. Wennemers. Frame Shifts Affect the Stability of Collagen Triple Helices. J. Am. Chem. Soc. 2022, 144, 18642
2b. Tomas Fiala, Emilia P. Barros, Rahel Heeb, Sereina Riniker, and Helma Wennemers. Predicting Collagen Triple Helix Stability through Additive Effects of Terminal Residues and Caps. Angew. Chem. Int. Ed. 2023, 62, 3, e202214728

3. J. Egli, C. Siebler, B. Maryasin, R. S. Erdmann, C. Bergande, C. Ochsenfeld, and H. Wennemers. pH-Responsive Aminoproline-Containing Collagen Triple Helices. Chem. Eur. J., 2017, 23, ,33, 7938-7944

4. J. Egli, C. Esposito, M. Müri, S. Riniker, and H. Wennemers. Influence of Lipidation on the Folding and Stability of Collagen Triple Helices—An Experimental and Theoretical Study. J. Am. Chem. Soc. 2021, 143, 15, 5937–5942

5. N. B. Hentzen, V. Islami, M. Köhler, R. Zenobi, and H. Wennemers. A Lateral Salt Bridge for the Specific Assembly of an ABC-Type Collagen Heterotrimer. J. Am. Chem. Soc., 2020, 142, 2208

6. M. R. Aronoff, P. Hiebert, N. B. Hentzen, S. Werner, and H. Wennemers. Imaging and Targeting LOX-Mediated Tissue Remodeling with a Reactive Collagen Peptide. Nat. Chem. Biol. 2021, 17, 8, 865