PUGNAc explained

PUGNAc is a 1,5-hydroximolactone, acting as an inhibitor of a variety of N-acetylhexosaminidases.^[1] It was long thought that increased levels of O-GlcNAc in human cells lead to Type II diabetes. O-GlcNAc levels were artificially raised with PUGNAc, which inhibits O-GlcNAcase, a beta-exo-N-acetylhexosaminidase which cleaves beta-O-linked-N-acetylglucosamine residues from glycoproteins. As a result of this inhibition, a type II diabetic phenotype was observed. Recent pharmacological studies using a more selective O-GlcNAcase inhibitor did not see this effect. However, genetic manipulation of O-GlcNAc levels is consistent with the effects observed by PUGNAc, namely insulin resistance upon elevation of O-GlcNAc levels.^[2]

Fictional references

PUGNAc was used by Michael Scofield in the television series Prison Break to keep his blood sugar level high to appear diabetic.^[3]

Further reading

• Vosseller K, Wells L, Lane MD, Hart GW . Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes . Proceedings of the National Academy of Sciences of the United States of America . 99 . 8 . 5313–8 . April 2002 . 11959983 . 122766 . 10.1073/pnas.072072399 .

Notes and References

1. Book: Cox NJ, Meister TR, Boyce M . Chemical biology of O-GlcNAc glycosylation . https://books.google.com/books?id=WmwoDwAAQBAJ&dq=PUGNAc&pg=PT102 . Tan Z, Wang LX. Chemical biology of glycoproteins . March 2017 . United Kingdom . Royal Society of Chemistry . 10.1039/9781782623823-00094 . 978-1-78801-122-8.
2. Cheng SS, Mody AC, Woo CM . 2024-11-07 . Opportunities for Therapeutic Modulation of O-GlcNAc . Chemical Reviews . en . 10.1021/acs.chemrev.4c00417 . 0009-2665.
3. Season 1, episode 1