DPP-4 Cleaves alpha/beta-Peptide Bonds Substrate Specificity and Half-Lives /
The incorporation of beta-amino acids into a peptide sequence has gained particular attention as beta- and alpha/beta-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specifi...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2020
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| Sorozat: | CHEMBIOCHEM
21 No. 14 |
| Tárgyszavak: | |
| doi: | 10.1002/cbic.202000050 |
| mtmt: | 31371344 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/22614 |
| Tartalmi kivonat: | The incorporation of beta-amino acids into a peptide sequence has gained particular attention as beta- and alpha/beta-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specificity but at a much slower rate compared to alpha-peptide bonds. In this study, a series of analogs of dipeptidyl peptidase-4 (DPP-4) substrate inhibitors were synthesized in order to investigate whether beta-amino acid homologation at the scissile bond could be a valid approach to improving peptide stability towards DPP-4 degradation. DPP-4 cleaved the alpha/beta-peptide bond after the N-terminal penultimate Pro with a broad specificity and retained full activity regardless of the beta(3)-amino acid side chain and peptide length. Significantly improved half-lives were observed for beta(3)Ile-containing peptides. Replacing the penultimate Pro with a conformationally constrained Pro mimetic led to proteolytic resistance. DPP-4 cleavage of alpha/beta-peptide bonds with a broad promiscuity represents a new insight into the stability of peptide analogs containing beta-amino acids as such analogs were thought to be stable towards enzymatic degradation. |
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| Terjedelem/Fizikai jellemzők: | 2060-2066 |
| ISSN: | 1439-4227 |