Article
Biochemistry & Molecular Biology
Francesca Clemente, Macarena Martinez-Bailen, Camilla Matassini, Amelia Morrone, Silvia Falliano, Anna Caciotti, Paolo Paoli, Andrea Goti, Francesca Cardona
Summary: This study reports the synthesis of five new trihydroxypiperidine iminosugars and identifies compound 12 as a potential therapeutic agent with chaperoning properties for GM1 gangliosidosis patients.
Article
Chemistry, Multidisciplinary
Sha Zhu, Yerri Jagadeesh, Anh Tuan Tran, Shuki Imaeda, Alisdair Boraston, Dominic S. Alonzi, Ana Poveda, Yongmin Zhang, Jerome Desire, Julie Charollais-Thoenig, Stephane Demotz, Atsushi Kato, Terry D. Butters, Jesus Jimenez-Barbero, Matthieu Sollogoub, Yves Bleriot
Summary: In the study, a pharmacological chaperone approach was explored to enhance the activity of NAGLU in patient fibroblasts affected by Mucopolysaccharidosis type IIIB. By synthesizing a library of iminosugar C-glycosides, it was found that a non-functionalized and wrongly configured beta-homoiminosugar acted as the most promising pharmacological chaperone, promoting a 2.4 fold activity enhancement of mutant NAGLU at its optimal concentration.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Medicinal
Atsushi Kato, Izumi Nakagome, Uta Kanekiyo, Tian-Tian Lu, Yi-Xian Li, Kosuke Yoshimura, Mana Kishida, Kenta Shinzawa, Tomoki Yoshida, Nobutada Tanaka, Yue-Mei Jia, Robert J. Nash, George W. J. Fleet, Chu-Yi Yu
Summary: In recent years, pharmacological chaperones have been recognized as thermodynamic stabilizers in combination therapy. This study focused on designing a high-affinity ligand for lysosomal acid alpha-glucosidase (GAA) using alkyl branches on 1-deoxynojirimycin (DNJ). The results showed that 5-C-heptyl-DNJ significantly improved the stability of recombinant human acid alpha-glucosidase (rhGAA) and increased intracellular GAA activities in cells from Pompe disease patients.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Andres G. Santana, Kyle Robinson, Chelsea Vickers, Matthew C. Deen, Hong-Ming Chen, Stephen Zhou, Ben Dai, Maria Fuller, Alisdair B. Boraston, David J. Vocadlo, Lorne A. Clarke, Stephen G. Withers
Summary: In this study, we synthesized a novel pharmacological chaperone that improves the low enzyme activity in Gaucher disease patients. Cell and animal experiments demonstrated the effectiveness of this chaperone in enhancing enzymatic activity, suggesting its potential therapeutic value.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Atsushi Kato, Izumi Nakagome, Maki Kise, Kousuke Yoshimura, Nobutada Tanaka, Robert J. Nash, George W. J. Fleet, Yota Kobayashi, Hayato Ikeda, Takuya Okada, Naoki Toyooka
Summary: This study presents a strategy for designing a practical ligand for lysosomal acid alpha-glucosidase (GAA) with a focus on N-alkyl derivatives of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB). The optimized N-4'-(p-trifluoromethylphenyl)butyl-DAB (5g) showed significantly higher affinity for GAA compared to N-butyl-DAB (3f). Docking analysis revealed the accommodation of the phenyl group of 5g in a lipophilic pocket and the stabilizing effect of the p-trifluoromethyl group.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Macarena Martinez-Bailen, Francesca Clemente, Camilla Matassini, Francesca Cardona
Summary: Pharmaceutical chaperones (PCs) are small compounds that can bind and stabilize misfolded proteins, helping them regain their native conformation and biological activity. They are especially beneficial in treating lysosomal storage disorders (LSDs) caused by genetic mutations. However, despite the importance of the GCase enzyme in treating LSDs and neurological disorders, no PC for this enzyme has been approved for market use. This review highlights the efforts made in the past 7 years to identify new PCs for the GCase enzyme, with a focus on glycomimetic-based compounds.
Article
Chemistry, Multidisciplinary
Arnold E. Stuetz, Martin Thonhofer, Patrick Weber, Andreas Wolfsgruber, Tanja M. Wrodnigg
Summary: The article presents a brief survey on selected beta-galactosidase inhibitors as potential pharmacological chaperones for G(M1)-gangliosidosis and Morquio B associated mutants of human lysosomal beta-galactosidase, highlighting recent developments in this specific area of lysosomal storage disorders and orphan diseases.
Article
Chemistry, Medicinal
Hung-Yi Lin, Shih-Ying Chang, Huang-Yi Li, Chia-Chun Cheng, Chih-Kuang Chuang, Hsiang-Yu Lin, Shuan-Pei Lin, Wei-Chieh Cheng
Summary: This study describes the synthesis of L-iduronic acid (IdoA)-and imino-IdoA-typed C-glycosides for modulating alpha-L-iduronidase (IDUA) activity. The IdoA-typed C-glycosides showed greater potency than the imino-IdoA analogs in enzyme inhibition studies, with the most potent C-glycoside 27c exhibiting an IC50 value of 1 μM. Co-treatment of 12 with rh-alpha-IDUA in mucopolysaccharidosis type I (MPS I) fibroblasts resulted in a significant increase in IDUA activity and reduction of accumulated heparan sulfate (HS), indicating the feasibility and promise of small molecules as rh-alpha-IDUA stabilizers for improving enzyme replacement therapy (ERT) efficacy in MPS I.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biotechnology & Applied Microbiology
Stefan J. Marciniak, Joseph E. Chambers, David Ron
Summary: Research on drug-like molecules targeting ER stress and UPR has made progress, but limitations still exist. Understanding these limitations is crucial for the development of these molecules into therapeutic drugs.
NATURE REVIEWS DRUG DISCOVERY
(2022)
Article
Chemistry, Multidisciplinary
My Lan Tran, Marc Borie-Guichot, Virginie Garcia, Abdelouahd Oukhrib, Yves Genisson, Thierry Levade, Stephanie Ballereau, Cedric-Olivier Turrin, Cecile Dehoux
Summary: The researchers synthesized phosphorus dendrimers with a cyclotriphosphazene core and decorated with monofluorocyclooctyne units. They grafted N-hexyl deoxynojirimycin inhibitors onto the surface of dendrimers. These synthesized iminosugars were tested as multivalent inhibitors of enzymes associated with Gaucher and Pompe lysosomal storage diseases, showing higher potency than the reference inhibitor. These dendrimers were also evaluated as pharmacological chaperones against Gaucher disease, exhibiting increased enzyme activity in Gaucher cells.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Tereza Cristina Santos Evangelista, Oscar Lopez, Adrian Puerta, Miguel X. Fernandes, Sabrina Baptista Ferreira, Jose M. Padron, Jose G. Fernandez-Bolanos, Magne O. Sydnes, Emil Lindback
Summary: The synthesis of four heterodimers connecting a 1-deoxynojirimycin moiety with a benzotriazole scaffold using the copper(I)-catalysed azide-alkyne cycloaddition was reported. These heterodimers showed preferential inhibition against butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE) in the micromolar concentration range. The most potent inhibitor of BuChE demonstrated a mixed inhibition mode, with the benzotriazole and 1-deoxynojirimycin moiety accommodated in the catalytic anionic site and peripheral anionic site of AChE, respectively. However, the binding mode to BuChE was different, with the benzotriazole moiety accommodated in the catalytic anionic site.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Hongjian Gao, Ao Fan
Summary: A green synthetic route was developed for the synthesis of enzyme active hydroxypiperidine iminosugars, resulting in good overall yields. Heterogeneous catalysts and environmentally friendly reagents were utilized in critical reactions, with the Au/Al2O3 catalyst being easily recovered and reused without loss of activity.
SCIENTIFIC REPORTS
(2021)
Correction
Chemistry, Organic
Irene Conforti, Alberto Marra
Summary: This paper corrects the information about iminosugars as glycosyltransferase inhibitors, providing new perspectives and evidence.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Haibo Wang, Senling Tang, Guoqing Zhang, Yang Pan, Wei Jiao, Huawu Shao
Summary: A series of N-substituted iminosugar C-glycosides were synthesized and tested for their inhibition on alpha-glucosidase. Compound 6e showed promise as a potent inhibitor of alpha-glucosidase and may be classified as an uncompetitive inhibitor based on enzymatic kinetic assays. The study of structure-activity relationships of these iminosugars serves as a starting point for the discovery of new alpha-glucosidase inhibitors.
Article
Chemistry, Organic
Roger A. Ashmus, Yang Wang, Manuel Gonzalez-Cuesta, Dustin T. King, Ben Tiet, Pierre-Andre Gilormini, Jose M. Garcia Fernandez, Carmen Ortiz Mellet, Robert Britton, David J. Vocadlo
Summary: The study focuses on the rational design and synthesis of C2-modified DGJ analogues to selectively inhibit human GALA over other glycosidases. The most selective inhibitor 7c was prepared from non-carbohydrate materials and demonstrated its effectiveness in reducing disease-relevant glycolipid Gb3 levels in Fabry patient cells.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Meeting Abstract
Biochemical Research Methods
Agnieszka Loboda, Szymon Czauderna, Olga Mucha, Paulina Podkalicka, Maria Czarnek, Anna Biela, Mateusz Mieczkowski, Jacek Stepniewski, Neli Kachamakova-Trojanowska, Alicja Jozkowicz, Jozef Dulak
Article
Chemistry, Medicinal
Sophie Front, Anna Biela-Banas, Patricie Burda, Diana Ballhausen, Katsumi Higaki, Anna Caciotti, Amelia Morrone, Julie Charollais-Thoenig, Estelle Gallienne, Stephane Demotz, Olivier R. Martin
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Olga Mucha, Paulina Podkalicka, Maria Czarnek, Anna Biela, Mateusz Mieczkowski, Neli Kachamakova-Trojanowska, Jacek Stepniewski, Alicja Jozkowicz, Jozef Dulak, Agnieszka Loboda
ACTA BIOCHIMICA POLONICA
(2018)
Article
Biochemistry & Molecular Biology
Anna Biela-Banas, Estelle Gallienne, Olivier R. Martin
CARBOHYDRATE RESEARCH
(2013)
Article
Chemistry, Medicinal
Anna Biela-Banas, Farah Oulaidi, Sophie Front, Estelle Gallienne, Kyoko Ikeda-Obatake, Naoki Asano, David A. Wenger, Olivier R. Martin
Article
Chemistry, Organic
Anna Biela, Farah Oulaidi, Estelle Gallienne, Marcin Gorecki, Jadwiga Frelek, Olivier R. Martin
Article
Biochemistry & Molecular Biology
Olga Mucha, Paulina Podkalicka, Maciej Mikulski, Szymon Barwacz, Kalina Andrysiak, Anna Biela, Mateusz Mieczkowski, Neli Kachamakova-Trojanowska, Damian Ryszawy, Arkadiusz Bialas, Bozena Szelazek, Przemyslaw Grudnik, Eliza Majewska, Kinga Michalik, Krzysztof Jakubiec, Marcin Bien, Natalia Witkowska, Karolina Gluza, Dariusz Ekonomiuk, Kamil Sitarz, Michal Galezowski, Krzysztof Brzozka, Grzegorz Dubin, Alicja Jozkowicz, Jozef Dulak, Agnieszka Loboda
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2019)
Article
Biochemistry & Molecular Biology
Paulina Podkalicka, Olga Mucha, Szczepan Kruczek, Anna Biela, Kalina Andrysiak, Jacek Stepniewski, Maciej Mikulski, Michal Galezowski, Kamil Sitarz, Krzysztof Brzozka, Alicja Jozkowicz, Jozef Dulak, Agnieszka Loboda
Article
Genetics & Heredity
Ting-Yu Lin, Robert Smigiel, Bozena Kuzniewska, Joanna J. Chmielewska, Joanna Kosinska, Mateusz Biela, Anna Biela, Anna Koscielniak, Dominika Dobosz, Izabela Laczmanska, Andrzej Chramiec-Glabik, Jakub Jezowski, Jakub Nowak, Monika Gos, Sylwia Rzonca-Niewczas, Magdalena Dziembowska, Rafal Ploski, Sebastian Glatt
Summary: This study reveals that genomic variants in the PUS3 gene can lead to reduced pseudouridine (psi) levels in patient cells, providing a molecular explanation for the observed clinical phenotypes.
Review
Biochemistry & Molecular Biology
Nour-el-Hana Abbassi, Anna Biela, Sebastian Glatt, Ting-Yu Lin
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Andre R. A. Marques, Lianne I. Willems, Daniela Herrera Moro, Bogdan I. Florea, Saskia Scheij, Roelof Ottenhoff, Cindy P. A. A. van Roomen, Marri Verhoek, Jessica K. Nelson, Wouter W. Kallemeijn, Anna Biela-Banas, Olivier R. Martin, M. Begona Cachon-Gonzalez, Nee Na Kim, Timothy M. Cox, Rolf G. Boot, Herman S. Overkleeft, Johannes M. F. G. Aerts
Article
Chemistry, Organic
Geeta Devi Yadav, Pooja Chaudhary, Balaram Pani, Surendra Singh
Summary: Chiral transition metal complexes with privileged ligands are efficient catalysts for various asymmetric organic transformations. Transition metal complexes of C1-symmetric pyrrolidine-based ligands have been widely used in asymmetric organic reactions. However, a comprehensive review article on the transition metal complexes of chiral C1-symmetric pyrrolidine-based ligands derived from (L)-proline has not been published.
TETRAHEDRON LETTERS
(2024)