O-N intramolecular acyl migration reaction in the development of prodrugs and the synthesis of difficult sequence-containing bioactive peptides

Biopolymers
Youhei SohmaYoshiaki Kiso

Abstract

N-Ointramolecular acyl migration in Ser- or Thr-containing peptides is a well-known side reaction in peptide chemistry. It results in the mutual conversion of ester and amide bonds. Our medicinal chemistry study focused on the fact that the O-acyl product can be readily converted to the original N-acyl form under neutral or slightly basic conditions in an aqueous buffer and the liberated ionized amino group enhances the water solubility of O-acyl products. Because of this, we have developed a novel class of "O-N intramolecular acyl migration"-type water-soluble prodrugs of HIV-1 protease inhibitors. These prodrugs released the parent drugs via a simple chemical mechanism with no side reaction. In this study, we applied this strategy to important cancer chemotherapeutic agents, paclitaxel and its derivatives, to develop water-soluble taxoid prodrugs, and found that these prodrugs, 2'-O-isoform of taxoids, showed promising results with higher water solubility and proper kinetics in their parent drug formation by a simple pH-dependent chemical mechanism with O-N intramolecular acyl migration. These results suggest that this strategy would be useful in toxicology and medical economics. After the successful application of O-N intram...Continue Reading

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Citations

Feb 23, 2013·Organic & Biomolecular Chemistry·Waleed M HusseinMariusz Skwarczynski
Oct 18, 2012·Chemical Communications : Chem Comm·Jean-Christophe M Monbaliu, Alan R Katritzky
Jul 14, 2007·Advanced Drug Delivery Reviews·Valentino J Stella, Kwame W Nti-Addae
Mar 12, 2005·Journal of Peptide Science : an Official Publication of the European Peptide Society·Youhei SohmaYoshiaki Kiso
Sep 4, 2008·Archiv der Pharmazie·Jeffrey-Tri NguyenYoshiaki Kiso
Nov 26, 2008·Chembiochem : a European Journal of Chemical Biology·Atsuhiko TaniguchiYoshiaki Kiso
Sep 7, 2007·Journal of Peptide Science : an Official Publication of the European Peptide Society·Atsuhiko TaniguchiYoshiaki Kiso
Jan 20, 2007·Biopolymers·Youhei SohmaYoshiaki Kiso
Sep 4, 2008·Angewandte Chemie·Miquel Vila-PerellóTom W Muir
Nov 30, 2006·Journal of Peptide Science : an Official Publication of the European Peptide Society·Youhei SohmaYoshiaki Kiso
Mar 11, 2011·Journal of Neurochemistry·István FöldiTamás Janáky
Mar 21, 2013·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Youhei Sohma, Yoshiaki Kiso
Apr 20, 2010·Journal of Peptide Science : an Official Publication of the European Peptide Society·Irene Coin
Mar 29, 2014·Chemical Biology & Drug Design·Oliwia FrączakAleksandra Olma
Nov 6, 2007·Carbohydrate Research·Silvana PedatellaGiovanni Palumbo
Jun 30, 2006·Bioorganic & Medicinal Chemistry Letters·Mariusz SkwarczynskiYoshiaki Kiso
Jul 26, 2005·Bioorganic & Medicinal Chemistry·Youhei SohmaYoshiaki Kiso
Mar 31, 2015·Carbohydrate Polymers·Ruoran Zhang, Kevin J Edgar
Jul 17, 2018·Journal of Peptide Science : an Official Publication of the European Peptide Society·Risa TakayamaFayna Garcia-Martin
May 31, 2019·Chembiochem : a European Journal of Chemical Biology·Melrose Mailig, Fa Liu
Feb 18, 2020·Science Advances·Mariusz SkwarczynskiIstvan Toth
Feb 10, 2021·Chemistry : a European Journal·Liam S Fitzgerald, Miriam L O'Duill
Sep 11, 2018·Biomacromolecules·Chengzhe Gao, Kevin J Edgar
Dec 8, 2006·Journal of Medicinal Chemistry·Mariusz SkwarczynskiYoshiaki Kiso
Mar 11, 2006·The Journal of Organic Chemistry·Mariusz SkwarczynskiYoshiaki Kiso

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