1353018-32-2Relevant academic research and scientific papers
Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 5′-hydroxy-6′-deoxy-amanitin
Matinkhoo, Kaveh,Perrin, David M.,Pryyma, Alla,Wong, Antonio A. W. L.
, p. 11927 - 11935 (2020)
Appreciating the need to access synthetic analogs of amanitin, here we report the synthesis of 5′-hydroxy-6′-deoxy-amanitin, a novel, rationally-designed bioactive analog and constitutional isomer of α-amanitin, that is anticipated to be used as a payload for antibody drug conjugates. In completing this synthesis, we meet the challenge of diastereoselective sulfoxidation by presenting two high-yielding and diastereoselective sulfoxidation approaches to afford the more toxic (R)-sulfoxide.
Synthesis of redox-active fluorinated 5-hydroxytryptophans as molecular reporters for biological electron transfer
Ohler, Amanda,Long, Hanna,Ohgo, Kei,Tyson, Kristin,Murray, David,Davis, Amanda,Whittington, Chris,Hvastkovs, Eli G.,Duffy, Liam,Haddy, Alice,Sargent, Andrew L.,Allen, William E.,Offenbacher, Adam R.
, p. 3107 - 3110 (2021)
Fluorinated 5-hydroxytryptophans (Fn-5HOWs) were synthesized in gram scale quantities and incorporated into a β-hairpin peptide and the protein azurin. The redox-active Fn-5HOWs exhibit unique radical spectroscopic signatures that expand the function of 5HOW as probes for biological electron transfer.
Synthesis of peptides containing 5-hydroxytryptophan, oxindolylalanine, N-formylkynurenine and kynurenine
Todorovski, Toni,Fedorova, Maria,Hennig, Lothar,Hoffmann, Ralf
, p. 256 - 262 (2012/01/13)
ROS, continuously produced in cells, can reversibly or irreversibly oxidize proteins, lipids, and DNA. At the protein level, cysteine, methionine, tryptophan, and tyrosine residues are particularly prone to oxidation. Here, we describe the solid phase synthesis of peptides containing four different oxidation products of tryptophan residues that can be formed by oxidation in proteins in vitro and in vivo: 5-HTP, Oia, Kyn, and NFK. First, we synthesized Oia and NFK by selective oxidation of tryptophan and then protected the ${bf alpha}$-amino group of both amino acids, and the commercially available 5-HTP, with Fmoc-succinimide. High yields of Fmoc-Kyn were obtained by acid hydrolysis of Fmoc-NFK. All four Fmoc derivatives were successfully incorporated, at high yields, into three different peptide sequences from skeletal muscle actin, creatin kinase (M-type), and ${bf beta}$-enolase. The correct structure of all modified peptides was confirmed by tandem mass spectrometry. Interestingly, isobaric peptides containing 5-HTP and Oia were always well separated in an acetonitrile gradient with TFA as the ion-pair reagent on a C18-phase. Such synthetic peptides should prove useful in future studies to distinguish isobaric oxidation products of tryptophan.
