Related Experiment Video
Updated: Mar 7, 2026
09:27
Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues
Published on: February 17, 2017
10.8K
Rational design of reversible inhibitors for trehalose 6-phosphate phosphatases
Chunliang Liu1, Debra Dunaway-Mariano1, Patrick S Mariano1
1Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM 87131, USA.
European Journal of Medicinal Chemistry
|February 14, 2017
Summary
Researchers developed novel aryl d-glucopyranoside 6-sulfates as potential inhibitors for trehalose 6-phosphate phosphatase (T6PP). These compounds show promise for developing new antibacterial, antifungal, and antihelminthic therapeutics by targeting T6PP enzymes.
Area of Science:
- Biochemistry
- Medicinal Chemistry
- Enzymology
Background:
- Environmental stress induces trehalose biosynthesis, crucial for organism survival.
- Trehalose 6-phosphate phosphatase (T6PP) is a key enzyme in this pathway.
- T6PP is a validated drug target for various infectious diseases.
Purpose of the Study:
- To design, synthesize, and evaluate aryl d-glucopyranoside 6-sulfates as T6PP inhibitors.
- To explore the potential of these compounds as therapeutic agents against pathogens.
Main Methods:
- Synthesis of a library of aryl d-glucopyranoside 6-sulfates.
- Steady-state kinetic assays to determine inhibition constants (Ki).
- Evaluation of inhibitor activity against T6PP orthologs from diverse pathogens.
Main Results:
- Identified 4-n-octylphenyl α-d-glucopyranoside 6-sulfate (9a) as a potent T6PP inhibitor.
- Compound 9a exhibited low micromolar binding affinities (Ki = 5.3 ± 0.6 μM for B. malayi T6PP).
- Demonstrated binding specificity of 9a against related phosphatases.
Conclusions:
- Aryl d-glucopyranoside 6-sulfates are effective prototypes for T6PP inhibitors.
- Compound 9a shows significant potential for therapeutic development.
- Further optimization could lead to tailored second-generation T6PP inhibitors.
