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3-(3-methyl-3-diazirinyl)-L-alanine

Base Information
  • Chemical Name:3-(3-methyl-3-diazirinyl)-L-alanine
  • CAS No.:851960-91-3
  • Molecular Formula:C5H9N3O2
  • Molecular Weight:143.145
  • Hs Code.:
3-(3-methyl-3-diazirinyl)-L-alanine

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Chemical Property of 3-(3-methyl-3-diazirinyl)-L-alanine
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Refernces

Photo-leucine incorporation reveals the target of a cyclodepsipeptide inhibitor of cotranslational translocation

10.1021/ja076250y

The research aims to identify the target protein of HUN-7293, a fungal cyclodepsipeptide that inhibits the cotranslational translocation of certain proteins into the endoplasmic reticulum (ER). The study employs photoaffinity labeling, a technique that uses light-activated molecules to bind to their targets, to pinpoint the specific protein targeted by HUN-7293. The researchers synthesized a photoaffinity probe (2) by incorporating photo-leucine, an amino acid with a photoreactive diazirine side chain, into the structure of HUN-7293. They also added a propargyl substituent to enable click chemistry, a method for attaching a fluorescent reporter to the cross-linked protein. The probe was used to irradiate a mixture of ER microsomes, and the resulting cross-linked proteins were identified using click chemistry with a rhodamine-azide reporter. The study concluded that Sec61R, the largest subunit of the Sec61 complex, is the primary target of HUN-7293. This finding was confirmed through immunoprecipitation and reconstitution experiments with proteoliposomes. The research highlights the effectiveness of photo-leucine in identifying protein targets and suggests that Sec61R is the key protein disrupted by HUN-7293, providing insights into the mechanism of cotranslational translocation inhibition.

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