Green mamba peptide targets type-2 vasopressin receptor against polycystic kidney disease - Université de Montpellier
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2017

Green mamba peptide targets type-2 vasopressin receptor against polycystic kidney disease

Résumé

Significance Polycystic kidney diseases (PKDs) are genetic disorders in which multiple cysts grow in kidneys, leading to end-stage renal failure. Vasopressin antagonists (vaptans) currently used to treat PKDs have side effects due to liver toxicity. We report the characterization of Mambaquaretin-1, a Kunitz-fold polypeptide isolated from mamba venom that selectively and fully inhibits three major signaling pathways of the vasopressin type-2 receptor. Mambaquaretin-1 induces a purely aquaretic effect on mice and reduces cyst development in a mouse model. We produced mambaquaretin-1 by peptide synthesis and determined its X-ray structure, its binding mode, and functional properties. With high selectivity and without toxic metabolic byproducts associated with its peptidic nature, mambaquaretin-1 could become the preferential treatment for these disorders.

Dates et versions

hal-04467166 , version 1 (20-02-2024)

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Citer

Justyna Ciolek, Helen Reinfrank, Loïc Quinton, Say Viengchareun, Enrico Stura, et al.. Green mamba peptide targets type-2 vasopressin receptor against polycystic kidney disease. Proceedings of the National Academy of Sciences of the United States of America, 2017, 114 (27), pp.7154-7159. ⟨10.1073/pnas.1620454114⟩. ⟨hal-04467166⟩
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