Oral 9th Venoms to Drugs 2026

Total Chemical Synthesis of HCRG21, a Venom-derived Inhibitor of TRPV1 with Therapeutic Potential (147674)

Paul Harris 1 2 , Jinwei Sun 1 , Martin Middleditch 1 , Young Paul 1 , Kerry Loomes 1
  1. School of Biological Sciences, The University of Auckland, Auckland 1142, New Zealand
  2. School of Chemical Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland 1142, New Zealand

HCRG21, a recently discovered Kunitz-type peptide from the venom of the sea anemone Heteractis crispa, comprises 56 amino acids and stabilized by three disulfide bonds and has been shown to be a TRPV1 antagonist1 .  We outline a fully chemical synthesis route to HCRG21, using SPPS, native chemical ligation and selective oxidative folding followed by characterization by microED , enzymatic digestion and mass spectrometry.  We also discuss its activity against the related TRPV4 receptor, which is involved in metabolic regulation.

 

1. Monastyrnaya, M.; Peigneur, S.; Zelepuga, E.; Sintsova, O.; Gladkikh, I.; Leychenko, E.; Isaeva, M.; Tytgat, J.; Kozlovskaya, E. Kunitz-Type Peptide HCRG21 from the Sea Anemone Heteractis crispa Is a Full Antagonist of the TRPV1 Receptor. Mar. Drugs 2016, 14, 229. https://doi.org/10.3390/md14120229