Hyperstable, Minimal-Length, and Blunt-Ended Collagen Heterotrimers
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
891009
Marie Sklodowska-Curie
200020_207505
Swiss National Science Foundation - Switzerland
200020_178765
Swiss National Science Foundation - Switzerland
PubMed
40344344
DOI
10.1002/anie.202503353
Knihovny.cz E-zdroje
- Klíčová slova
- Collagen, Heterotrimer, Peptides, Salt bridge, Thermal stability,
- MeSH
- kolagen * chemie MeSH
- termodynamika MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kolagen * MeSH
Most natural collagens are heterotrimers-triple helices formed from three non-identical peptide strands. The design of synthetic heterotrimeric collagen is challenging since a mixture of three different peptides can form as many as 27 unique triple helices. Here, we present a general method for the assembly of collagen heterotrimers with a wide range of lengths, thermal stabilities, and strand arrangements driven by complementary interstrand salt bridges between (2S,4S)-4-aminoproline and aspartate residues. We show how kinetic trapping of undesired trimers can be overcome by adjusting the annealing conditions to obtain the target heterotrimeric helix selectively under thermodynamic control. The design rules and annealing methods allowed the creation of the most stable supramolecular heterotrimer (32 residues, Tm = 76 °C) and the shortest stable heterotrimer (17 residues, Tm = 19 °C) to date. Furthermore, frame-shifting enabled, for the first time, the creation of a collagen triple helix with blunt ends.
Department of Chemistry Faculty of Science Masaryk University Kamenice 5 Brno 625 00 Czech Republic
Laboratory of Organic Chemistry ETH Zürich Vladimir Prelog Weg 3 Zürich 8093 Switzerland
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