α-Mannosidase I Inhibitor Development Service at CD BioGlyco

CD BioGlyco aims to support clients in the research of therapeutic approaches to diseases. α-Mannosidase I has a certain conserved sequence. It is mainly distributed in the endoplasmic reticulum, Golgi apparatus, and some cell membranes. It is involved in N-glycan secretion and protein monitoring. It is mainly responsible for the trimming and processing of different types of mannose on the glycoprotein glycan chain during N-Glycosylation. Abnormalities in mannose metabolism are found to lead to serious diseases. We provide α-mannosidase I inhibitor development services. We focus on the following areas of inhibitor development.

• Substrate and product-based inhibitor development services

We screen compounds that are structurally similar to the substrates and products of α-mannosidase I action, including monosaccharide analogs, thiosugar derivatives, etc., and study their inhibitory activities. The screened inhibitors may be similar in spatial structure to the mannose cation formed during the hydrolysis of mannose. Or they have a high affinity for mannosidase, thus producing a strong inhibitory effect on the enzyme.

• Other aspects of inhibitor development services

It is found that the catalytic activity of α-mannosidase I is dependent on calcium ions. We try to inhibit its activity by regulating the concentration of calcium ions and others. Kifunensine is an α-mannosidase I inhibitor. We also try to synthesize other structurally similar Kifunensine derivatives and study their inhibitory effects. Specialized compound screening tools are also constructed to improve the efficiency of inhibitor screening.

Fig.1 Direction of α-mannosidase I inhibitor development. (CD BioGlyco)

Publication

Technology: Synthesis of Kifunensine derivatives

Journal: Angewandte Chemie - International Edition

IF: 16.823

Published: 2021

Results: In this study, a series of lectin constructs that can be used to find α-mannosidase I inhibitors were constructed. These lectin constructs were able to specifically detect inhibitor-induced changes in glycosylation for rapid screening for α-mannosidase I inhibitors. A series of kifunensine derivatives were tested for inhibition using these lectins. Finally, some compounds with better inhibitory effects were rapidly screened.

Fig.2 Kifunensine analogues. (Kurhade, et al., 2021)

Applications of α-Mannosidase I Inhibitor Development

• α-Mannosidase I is a potential target for cancer therapy. The development of α-mannosidase I inhibitors has an important role in the research of cancer therapy.
• The continuous development of α-mannosidase I inhibitors plays a crucial role in advancing research on therapeutic approaches to viral infections.
• The development of α-mannosidase I inhibitors has a crucial role in research into methods to reduce allograft rejection.

Highlights of Us

• We have developed appropriate functionalization tools to rapidly screen compounds with inhibitory activity against α-mannosidase I, which greatly improves development efficiency.
• The continuous development of α-mannosidase I inhibitors helps to find compounds with better inhibition and fewer side effects.

CD BioGlyco has been working on Glycosylation Inhibitor Development for many years. We aim to provide assistance and support to our partners in the research of disease treatment and biological mechanisms. Besides α-mannosidase I, we also provide α-Glucosidase II and α-Glucosidase I Inhibitor development services. Please feel free to contact us to inquire about the detailed process of inhibitor development. We are always ready to serve you.