IIB researchers develop method to unlock potential of heparin-based drugs

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Professor Jerry Turnbull

The blood-thinning drug heparin is used all over the world. But, the underlying sugar structures of heparin and the wider family of heparan sulfate sugars in cells have not been fully sequenced.

Research by Prof Jerry Turnbull, working with Dr Rebecca Miller (a former PhD student and postdoc in IIB, and now an Asst. Professor at University of Copenhagen) has resulted in development of an advanced mass spec-based method to unambiguously sequence these glycan structures in detail. This method has potential to reveal important biological functions and allow new drugs to be developed.

Heparan sulfate (HS) glycans play key roles in regulating many biological functions, including inflammation, neurodegeneration and tumor metastasis. Researchers are therefore intensively trying to understand the structures of heparan sulfates and their links to biological functions. The new method is called “Shotgun ion mobility mass spectrometry sequencing”, in which the glycan structures are fragmented and separated in the instrument, and fingerprinted compared to known standards, allows the complete determination of larger sequences. This means that detailed structure-activity studies can now be implemented for discovery of new HS-based drugs. The work was carried out in collaboration with researchers at Copenhagen University, Free University of Berlin, and Oxford University.

Continued development of the SIMMS method, and pioneering of its application to develop new uses of HS in medicine, will be undertaken with the recent award of an EU grant worth €3.8m to Prof Turnbull in a consortium that includes researchers from Copenhagen, Utrecht, Nijmegen and Stockholm.

The work is published in Nature Communications: https://www.nature.com/articles/s41467-020-15284-y.epdf