Search

Your search keyword '"Alla Pryyma"' showing total 2 results
Start Over Author "Alla Pryyma" Publisher american chemical society (acs)
2 results on '"Alla Pryyma"'

1. Scaling Amatoxin Synthesis with an Improved Route to (2S,3R,4R)-Dihydroxyisoleucine Exemplified by a Toxic, Clickable α-Amanitin Analogue

Author

David M. Perrin, Kaveh Matinkhoo, Chido M. Hambira, Brian O. Patrick, and Alla Pryyma

Subjects
endocrine system, animal structures, 010405 organic chemistry, Chemistry, Organic Chemistry, 010402 general chemistry, 01 natural sciences, Combinatorial chemistry, 0104 chemical sciences, 3. Good health, Turn (biochemistry), polycyclic compounds, Clickable, Amatoxin, Amino acid residue, Conjugate, Amanitin
Abstract

Here we report a scalable synthesis of the key amino acid residue, (2S,3R,4R)-4,5-dihydroxyisoleucine (DHIle) in α-amanitin, that in turn enables the scalable synthesis of an equipotent analogue, Asn(N-ethylazide)-S,6'-dideoxy-α-amanitin, suitable for CuAAC conjugation to empower studies on therapeutic antibody-drug conjugates.

Published
2021

2. Synthesis of the Death-Cap Mushroom Toxin α-Amanitin

Author

Mihajlo Todorovic, Brian O. Patrick, Alla Pryyma, Kaveh Matinkhoo, and David M. Perrin

Subjects
Models, Molecular, endocrine system, animal structures, Molecular Conformation, RNA polymerase II, CHO Cells, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biochemistry, Catalysis, Structure-Activity Relationship, Cricetulus, Colloid and Surface Chemistry, polycyclic compounds, medicine, Animals, Structure–activity relationship, Amanita phalloides, Alpha-Amanitin, Amanitin, Mushroom, Dose-Response Relationship, Drug, Bicyclic molecule, biology, 010405 organic chemistry, Toxin, Chemistry, Chinese hamster ovary cell, General Chemistry, Mycotoxins, biology.organism_classification, 0104 chemical sciences, biology.protein, Agaricales
Abstract

α-Amanitin is an extremely toxic bicyclic octapeptide isolated from the death-cap mushroom, Amanita phalloides. As a potent inhibitor of RNA polymerase II, α-amanitin is toxic to eukaryotic cells. Recent interest in α-amanitin arises from its promise as a payload for antibody-drug conjugates. For over 60 years, A. phalloides has been the only source of α-amanitin. Here we report a synthesis of α-amanitin, which surmounts the key challenges for installing the 6-hydroxy-tryptathionine sulfoxide bridge, enantioselective synthesis of (2 S,3 R,4 R)-4,5-dihydroxy-isoleucine, and diastereoselective sulfoxidation.

Published
2018

Catalog

Books, media, physical & digital resources
See catalog results