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Expanding peptide-cucurbit[7]uril interactions through selective N-terminal reductive alkylation
- Source :
- Current Research in Chemical Biology, Vol 2, Iss, Pp 100013-(2022)
- Publication Year :
- 2022
- Publisher :
- Elsevier, 2022.
-
Abstract
- Cucurbit[7]uril (CB[7]) is a supramolecular binding host for peptides and proteins with N-terminal Phe. However, the low occurrence of such peptides and proteins limits broader applications of this unique host-guest interaction. Here, we report a strategy to expand the scope of CB[7]-peptide interaction by site-specifically introducing N-terminal substitutions (e.g. benzyl groups) using reductive alkylation. N-terminal benzylated peptides have similar affinity to CB[7] as native peptides with N-terminal Phe and even stronger interactions can be achieved using better ligands. We further expanded this host-guest interaction to be stimuli responsive. By introducing benzyl carboxylate substituents, the CB[7]-peptide interaction shows pH-dependent binding. Furthermore, benzyl boronate substituents led to saccharide-dependent CB[7]-peptide interactions. We demonstrated that using this strategy to introduce stronger CB[7] binders to the N-terminus of human calcitonin (hCT) results in increased aggregation stability in the presence of CB[7]. This strategy to expand CB[7]-peptide interaction scope opens opportunities for future applications in peptides and proteins.
Details
- Language :
- English
- ISSN :
- 26662469
- Volume :
- 2
- Database :
- OpenAIRE
- Journal :
- Current Research in Chemical Biology
- Accession number :
- edsair.doi.dedup.....e86f1cc891457964ae1e5b7353d3df6f