Elucidating the active δ-opioid receptor crystal structure with peptide and small-molecule agonists

Better painkillers through structural biology

30 April 2020

The atomic structures of a pain-relieving receptor in complex with activating drugs could help spur the development of safer painkillers.

Opioid painkillers are highly addictive and prone to abuse, leading to the so-called opioid epidemic in the USA. There is thus a need for safer, less addictive opioid painkillers that target a different receptor.

Using X-ray crystallography, a team co-led by scientists from ShanghaiTech University mapped the structure of the delta-opioid receptor in its active state while bound to one of two different agonist drugs, one a short protein and one a small molecule.

The researchers determined the structural basis for drug recognition, receptor activation and drug selectivity — and how those key factors differ between protein- and chemical-based drugs.

The findings should inform future structure-based design of opioid painkillers with more favourable pharmacological profiles and fewer side effects than existing options.

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References

1. Science Advances 5, eaax9115 (2019). doi: 10.1126/sciadv.aax9115