Design, synthesis and glycosidase inhibition of DAB derivatives with C-4 peptide and dipeptide branches

Dong Zi; Yuna Shimadate; Jun-Zhe Wang; Atsushi Kato; Yi-Xian Li; Yue-Mei Jia; George W J Fleet; Chu-Yi Yu

doi:10.1039/d3ob00097d

Design, synthesis and glycosidase inhibition of DAB derivatives with C-4 peptide and dipeptide branches

Org Biomol Chem. 2023 Mar 29;21(13):2729-2741. doi: 10.1039/d3ob00097d.

Authors

Dong Zi^{1

2}, Yuna Shimadate³, Jun-Zhe Wang^{1

2}, Atsushi Kato³, Yi-Xian Li^{1

2}, Yue-Mei Jia^{1

2}, George W J Fleet⁴, Chu-Yi Yu^{1

2}

Affiliations

¹ Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. yucy@iccas.ac.cn.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ Department of Hospital Pharmacy, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. kato@med.u-toyama.ac.jp.
⁴ Chemistry Research Laboratory, Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, UK.

PMID: 36916165
DOI: 10.1039/d3ob00097d

Abstract

A series of DAB-peptide and DAB-dipeptide derivatives were synthesized from D-tartrate-derived nitrone 18. The DAB peptides 16 are derivatives of trans,trans-3,4-dihydroxy-L-proline. Glycosidase inhibition assay found four of them to be weak and selective bovine liver β-galactosidase inhibitors, and the C-2' methyl substituted compound 23b showed the most potent β-galactosidase inhibition (IC₅₀ = 0.66 μM). Molecular docking studies revealed different docking modes of compound 23b compared to those of other DAB-peptides, and partial similarity of compound 23b to DGJ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
C-Peptide
Cattle
Dipeptides*
Glycoside Hydrolases*
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
beta-Galactosidase

Substances

Glycoside Hydrolases
Dipeptides
C-Peptide
beta-Galactosidase