New method makes complex human milk sugars easier to make

1 min read

In a breakthrough that sheds light on the intricate mechanisms of cell signaling and immunity, researchers from Kuo's team have successfully developed an automated glycan assembly (AGA) method to synthesize sialylated human milk oligosaccharides (HMOs). By leveraging macrobicyclic sialic acid building blocks, they achieved reliable α(2,3)- and α(2,6)-sialylation on solid support, a feat that has long eluded solution-phase methods.

This achievement is particularly notable for its synthesis of fucosyldisialyllacto-N-tetraose (DSLNF II), a highly branched, fucosylated structure considered extremely challenging to synthesize. The team's innovative approach provides a reliable and scalable method for the production of sialylated glycans, which are pivotal in cell signaling, immunity, and pathogen interactions.

The researchers' strategy relies on a macrobicyclic sialic acid building block that allows for efficient and selective α(2,3)- and α(2,6)-sialylation. The use of solid support enables the controlled assembly of complex glycans, which are then subjected to an improved global deprotection protocol. This step is crucial in providing access to pure, functionalized complex glycans suitable for further biological studies.

The successful synthesis of a diverse collection of sialylated HMOs using this method opens up new avenues for biomedical research. It enables the preparation of collections of sialylated glycans that can be used to study their role in cell signaling, immunity, and pathogen interactions. This breakthrough serves as a testament to the power of automation in chemical synthesis, paving the way for further advances in our understanding of the complex relationships between glycan structures and biological processes.

1 min read

In a small laboratory, scientists carefully built blocks that would help them recreate the intricate structures found in human milk. These blocks were designed to mimic the sialic acids that cap the ends of many glycan chains, playing crucial roles in cell signaling and immunity. For years, researchers had struggled to synthesize these complex glycans efficiently using automated methods.

The team, led by Dr. Kuo, finally cracked the code with a novel approach that utilized macrobicyclic sialic acid building blocks. By leveraging this strategy, they were able to assemble nine diverse sialylated human milk oligosaccharides (HMOs), including one particularly challenging molecule called fucosyldisialyllacto-N-tetraose (DSLNF II). This breakthrough achieved what many had thought impossible: reliable α(2,3)- and α(2,6)-sialylation on solid support.

This discovery is significant not only for its technical achievement but also for the potential impact it holds. The sialylated glycans synthesized by this method are poised to become essential tools in biomedical research, enabling scientists to study the complex interactions between cells, pathogens, and the human immune system in greater detail than ever before.

1 min read

Imagine tiny building blocks that decorate the edges of cells like a special kind of address tag. These tags are called sialic acids, and they play a big role in how our bodies talk to each other - with our own immune system, and even with foreign invaders like bacteria. But making these tags using machines has been tricky.

Now, scientists have found a clever way to build these sialic acid tags quickly and reliably, using special blocks that fit together like Lego pieces. They used this method to create nine different types of complex sugars that are found in human milk, including one that is notoriously hard to make by hand. With their new technique, researchers can now study these sugars more easily - and maybe even discover new ways to keep our bodies healthy and strong.