PUGNAc

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]

In popular culture

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

References

1. ^ Cox NJ, Meister TR, Boyce M (March 2017). "Chemical biology of O-GlcNAc glycosylation". Chemical biology of glycoproteins. United Kingdom: Royal Society of Chemistry. pp. 94–149. doi:10.1039/9781782623823-00094. ISBN 978-1-78801-122-8.
2. ^ Cheng SS, Mody AC, Woo CM (2024-11-07). "Opportunities for Therapeutic Modulation of O-GlcNAc". Chemical Reviews. 124 (22): 12918–13019. doi:10.1021/acs.chemrev.4c00417. ISSN 0009-2665. PMID 39509538
3. ^ Season 1, episode 1

Further reading

• Vosseller K, Wells L, Lane MD, Hart GW (April 2002). "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. Bibcode:2002PNAS...99.5313V. doi:10.1073/pnas.072072399. PMC 122766. PMID 11959983