Abstract
Dipeptidyl peptidase III (DPP3) is a ubiquitously expressed zinc-dependent peptide cutting enzyme and selectively hydrolyses amide bonds to cleave N-terminal dipeptide fragments off of physiologically important oligopeptides. DPP3 has been found in a multitude of different types of cells and appears to be involved in various physiological processes (e.g. nociception, blood pressure control, protein turnover). Using the slowly converted peptide substrate tynorphin (VVYPW) as starting point, we have replaced the scissile bond with a fluoroethylene bioisostere to design ground state inhibitors, which led to the so far most effective peptide-based inhibitor of DPP3.
Original language | English |
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Article number | 116831 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 67 |
DOIs | |
Publication status | Published - 1 Aug 2022 |
Keywords
- Bioisostere
- Metalloenzyme
- Peptidomimetic
- Protease
- Small molecule inhibitor
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
Fields of Expertise
- Human- & Biotechnology
Cooperations
- BioTechMed-Graz