Biologically stable Trehalose analogue suitable for chemical modification 4-Trehalosamine

Trehalose is known as a disaccharide which is a glucose dimer. A lot of organisms in nature produce, store, and use trehalose to obtain sugar storage and desiccation tolerance. Mammalians including human have trehalose a specific glycosidase and utilize the enzyme to obtain energy from the sugar in food. It is also noticed the compound has the medication effectiveness. As an example of therapeutic efficacy of it against neurodegenerative diseases²⁾, it was reported that this compound extended lifespan in a transgenic mouse model of Huntington disease.⁴⁾ Although it was reported some studies to use trehalose as therapeutic or preventive medicines against fatty liver, arteriosclerosis, stroke, and diabetes, it is also known that it is unstable due to easy degradation by microorganisms.⁵⁾

Although 4-Trehalosamine which is substituted one hydroxyl group to the amino group in trehalose is expected to have similar efficacy of trehalose, it is high stable and cannot be hydrolyzed by trehalases in mammalian.⁵⁾ In oral administration to mice, it was reported that most of 4-Trehalosamine was excreted without degradation, modification, nor increase of blood glucose level after a part of it was circulated in blood. In bacterial culture, the amount of 4-Trehalosamine was decreasing because it might be caused by modification of the amino group in most cases. As it did not increase the growth rate of bacteria in media with low carbon source, however, it was confirmed that 4-Trehalosamine should not be hydrolyzed under the condition. In addition, it was observed that 4-Trehalosamine had protective effect from desiccation and inhibitory activity of starch retrogradation, which were similar or slightly stronger than trehalose.⁵⁾ Furthermore, its functions which trehalose does not have is pH buffering action at neutral pH stronger than Tris which is a well-known buffer solution. ⁵⁾. Therefore, 4-Trehalosamine might be expected to be more suitable for versatile applications than trehalose because of a moisturizing protectant with pH buffering action.
As production volume of 4-Trehalosamine is relatively high these days, it is expected to be close to the commercialization stage.
Trehalose derivatives are also synthesized from 4-Trehalosamine. One example of it is IMCTA-C14 which is a N-tetradecyl derivative and functions as a sugar surfactant.

IMCTA-C14 is a N-tetradecyl derivative of 4-Trehalosamine and functions similarly to a sugar surfactant with a complex of a sugar as a hydrophilic group and long chain aliphatic hydrocarbon. This compound is stable against trehalases in mammalian and was not observed hydrolysis by porcine one. In addition, it showed high efficiency of protein extraction and solubilization without denaturing proteins.
* See details of IMCTA-C14, click here!

Structure of IMCTA-C14 (Trifluoroacetate) (#15613)

Lentztrehalose A, B, and C are trehalose analogues isolated from the soilid-state culture of Lentzea sp. ML457-mF8. Unlike trehalose, these lentztrehalose analogues are stable to porcine kidney trehalase and not broken down by various microorganisms that metabolize trehalose.
* See details of Lentztrehalose, click here!