{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:27Z","timestamp":1787029107232,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regione Toscana (Bando Salute 2018)","award":["2022N9E847"],"award-info":[{"award-number":["2022N9E847"]}]},{"name":"Regione Toscana (Bando Salute 2018)","award":["20228S5LWY"],"award-info":[{"award-number":["20228S5LWY"]}]},{"name":"Ministry of University and Research (MUR)","award":["2022N9E847"],"award-info":[{"award-number":["2022N9E847"]}]},{"name":"Ministry of University and Research (MUR)","award":["20228S5LWY"],"award-info":[{"award-number":["20228S5LWY"]}]},{"name":"PRIN: PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE","award":["2022N9E847"],"award-info":[{"award-number":["2022N9E847"]}]},{"name":"PRIN: PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE","award":["20228S5LWY"],"award-info":[{"award-number":["20228S5LWY"]}]},{"name":"MUR\u2014Dipartimenti di Eccellenza 2023\u20132027 (DICUS 2.0)","award":["2022N9E847"],"award-info":[{"award-number":["2022N9E847"]}]},{"name":"MUR\u2014Dipartimenti di Eccellenza 2023\u20132027 (DICUS 2.0)","award":["20228S5LWY"],"award-info":[{"award-number":["20228S5LWY"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Morquio A syndrome is a lysosomal disorder caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine 6-sulfatase (GALNS, EC 3.1.6.4). Currently, enzyme replacement therapy (ERT) is used to treat Morquio A through the infusion of the recombinant enzyme VIMIZIM\u00ae (elosulfase alfa, BioMarin). Unfortunately, the recombinant enzyme exhibits low conformational stability in vivo. A promising approach to address this issue is the coadministration of recombinant human GALNS (rhGALNS) with a pharmacological chaperone (PC), a molecule that selectively binds to the misfolded protein, stabilizes its conformation, and assists in the restoration of the impaired function. We report in this work the synthesis of a library of multivalent glycomimetics exploiting the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between several dendrimeric scaffolds armed with terminal alkynes and azido ending iminosugars of different structures (pyrrolidines, piperidines, and pyrrolizidines) or simple azido ending carbohydrates as bioactive units. The biological evaluation identified pyrrolidine-based nonavalent dendrimers 1 and 36 as the most promising compounds, able both to bind the native enzyme with IC50 in the micromolar range and to act as enzyme stabilizers toward rhGALNS in a thermal denaturation study, thus identifying promising compounds for a combined PC\/ERT therapy.<\/jats:p>","DOI":"10.3390\/molecules30102222","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T08:41:12Z","timestamp":1747730472000},"page":"2222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring Multivalent Architectures for Binding and Stabilization of N-Acetylgalactosamine 6-Sulfatase"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1788-567X","authenticated-orcid":false,"given":"Maria Giulia","family":"Davighi","sequence":"first","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9899-0836","authenticated-orcid":false,"given":"Francesca","family":"Clemente","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2054-1862","authenticated-orcid":false,"given":"Giampiero","family":"D\u2019Adamio","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6924-5151","authenticated-orcid":false,"given":"Macarena","family":"Mart\u00ednez-Bail\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1236-826X","authenticated-orcid":false,"given":"Alessio","family":"Morano","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1081-533X","authenticated-orcid":false,"given":"Andrea","family":"Goti","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-8179","authenticated-orcid":false,"given":"Amelia","family":"Morrone","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology of Neurometabolic Diseases, Neuroscience Department, Meyer Children\u2019s Hospital IRCCS, Viale Pieraccini 24, 50139 Firenze, Italy"},{"name":"Department of Neurosciences, Psychology, Drug Research and Child Health University of Florence, Viale Pieraccini 24, 50139 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8336-383X","authenticated-orcid":false,"given":"Camilla","family":"Matassini","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"},{"name":"European Laboratory for Non-Linear Spectroscopy (LENS), University of Florence, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6766-4624","authenticated-orcid":false,"given":"Francesca","family":"Cardona","sequence":"additional","affiliation":[{"name":"Department of Chemistry \u201cU. Schiff\u201d (DICUS), University of Florence, Via della Lastruccia 3-13, 50019 Sesto Fiorentino, Italy"},{"name":"European Laboratory for Non-Linear Spectroscopy (LENS), University of Florence, 50019 Sesto Fiorentino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4492","DOI":"10.1039\/c3cs60089k","article-title":"Bridging lectin binding sites by multivalent carbohydrates","volume":"42","author":"Wittmann","year":"2013","journal-title":"Chem. Soc. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/cr500303t","article-title":"Glycomimetics versus multivalent glycoconjugates for the design of high affinity lectin ligands","volume":"115","author":"Cecioni","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Choi, S.-K. (2004). Synthetic Multivalent Molecules: Concepts and Biomedical Applications, Wiley.","DOI":"10.1002\/0471578908"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5207","DOI":"10.1039\/D0CC01135E","article-title":"Carbohydrate supramolecular chemistry: Beyond the multivalent effect","volume":"56","year":"2020","journal-title":"Chem. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"27215","DOI":"10.1021\/jacs.4c08818","article-title":"Sugar-Coated: Can Multivalent Glycoconjugates Improve upon Nature\u2019s Design?","volume":"146","author":"Leslie","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1039\/B815408B","article-title":"Multivalent iminosugars to modulate affinity and selectivity for glycosidases","volume":"7","author":"Diot","year":"2009","journal-title":"Org. Biomol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9894","DOI":"10.1039\/C5OB01405K","article-title":"Emerging trends in enzyme inhibition by multivalent nanoconstructs","volume":"13","author":"Kanfar","year":"2015","journal-title":"Org. Biomol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ymgme.2018.05.004","article-title":"Molecular genetics and metabolism, special edition: Diagnosis, diagnosis and prognosis of Mucopolysaccharidosis IVA","volume":"125","author":"Peracha","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_9","first-page":"45","article-title":"Current and emerging management options for patients with Morquio A syndrome","volume":"9","author":"Algahim","year":"2013","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s10545-013-9586-2","article-title":"Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): Presentation, diagnosis and management","volume":"36","author":"Solanki","year":"2013","journal-title":"J. Inher. Metab. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.3390\/ijms21041517","article-title":"Mucopolysaccharidosis IVA: Diagnosis, treatment, and management","volume":"21","author":"Sawamoto","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1358\/dot.2014.50.7.2177904","article-title":"Elosulfase alfa","volume":"50","author":"Haddley","year":"2014","journal-title":"Drugs Today"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s40265-014-0210-z","article-title":"Elosulfase alfa: First global approval","volume":"74","author":"Sanford","year":"2014","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3390\/ijms21020489","article-title":"Pharmacological chaperones: A therapeutic approach for diseases caused by destabilizing missense mutations","volume":"21","author":"Liguori","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1039\/C6CC01564F","article-title":"Glycomimetic-based pharmacological chaperones for lysosomal storage disorders: Lessons from Gaucher, GM1-gangliosidosis and Fabry diseases","volume":"52","year":"2016","journal-title":"Chem. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1021\/jm301557k","article-title":"Pharmacological Chaperones as Therapeutics for Lysosomal Storage Diseases","volume":"56","author":"Boyd","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1039\/C7SC04712F","article-title":"Tuning protein folding in lysosomal storage diseases: The chemistry behind pharmacological chaperones","volume":"9","author":"Pereira","year":"2018","journal-title":"Chem. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1021\/acschembio.6b00195","article-title":"Pharmacological Chaperones: Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases","volume":"11","author":"Convertino","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Khanna, R., Flanagan, J.J., Feng, J., Soska, R., Frascella, M., Pellegrino, L.J., Lun, Y., Guillen, D., Lockhart, D.J., and Valenzano, K.J. (2012). The Pharmacological Chaperone AT2220 Increases Recombinant Human Acid \u03b1-Glucosidase Uptake and Glycogen Reduction in a Mouse Model of Pompe Disease. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040776"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.bbrc.2008.02.125","article-title":"Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase","volume":"369","author":"Shen","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1038\/mt.2009.53","article-title":"The pharmacological chaperone N-butyldeoxynojirimycin enhances enzyme replacement therapy in Pompe disease fibroblasts","volume":"17","author":"Porto","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/mt.2011.271","article-title":"Co-administration With the Pharmacological Chaperone AT1001 Increases Recombinant Human \u03b1-Galactosidase A Tissue Uptake and Improves Substrate Reduction in Fabry Mice","volume":"20","author":"Benjamin","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1038\/mt.2014.138","article-title":"chaperone enhances blood \u03b1-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy","volume":"22","author":"Parenti","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/S1474-4422(21)00331-8","article-title":"Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): An international, randomised, double-blind, parallel-group, phase 3 trial","volume":"20","author":"Schoser","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/pros.23776","article-title":"Dihydrotestosterone inhibits arylsulfatase B and Dickkopf Wnt signaling pathway inhibitor (DKK)-3 leading to enhanced Wnt signaling in prostate epithelium in response to stromal Wnt3A","volume":"79","author":"Bhattacharyya","year":"2019","journal-title":"Prostate"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41392-022-01162-0","article-title":"Activated microglia nibbling glycosaminoglycans from spinal cord perineural nets: A new mechanism for neuropathic pain","volume":"7","author":"Claff","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1021\/acsmedchemlett.0c00042","article-title":"Bromocriptine as a Novel Pharmacological Chaperone for Mucopolysaccharidosis IV","volume":"11","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6175","DOI":"10.1021\/acs.jmedchem.9b00428","article-title":"Identification of Ezetimibe and Pranlukast as Pharmacological Chaperones for the Treatment of the Rare Disease Mucopolysaccharidosis Type IVA","volume":"62","author":"Hidalgo","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_29","first-page":"232","article-title":"Advances in the Development of Pharmacological Chaperones for the Mucopolysaccharidoses","volume":"21","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1016\/j.jmb.2012.08.020","article-title":"The Structure of Human GALNS Reveals the Molecular Basis for Mucopolysaccharidosis IV A","volume":"423","author":"Schutsky","year":"2012","journal-title":"J. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1002\/cbic.201402026","article-title":"The multivalent effect in glycosidase inhibition: A new, rapidly emerging topic in glycoscience","volume":"15","author":"Compain","year":"2014","journal-title":"Chem. Bio. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11616","DOI":"10.1002\/chem.201402537","article-title":"Multivalent inhibitors for carbohydrate-processing enzymes: Beyond the \u201clock-and-key\u201d concept","volume":"20","author":"Gouin","year":"2014","journal-title":"Chem. Eur. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5050","DOI":"10.1039\/C5NJ00462D","article-title":"Synthesis and biological properties of multivalent iminosugars","volume":"30","author":"Zelli","year":"2015","journal-title":"New J. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5407","DOI":"10.1016\/j.tetlet.2016.10.080","article-title":"Are enzymes sensitive to the multivalent effect? Emerging evidence with glycosidases","volume":"57","author":"Matassini","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/tcr.201900004","article-title":"Multivalent effect in glycosidase inhibition: The end of the beginning","volume":"20","author":"Compain","year":"2020","journal-title":"Chem. Rec."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"112173","DOI":"10.1016\/j.ejmech.2020.112173","article-title":"Synthesis of multimeric pyrrolidine iminosugar inhibitors of human \u03b2-glucocerebrosidase and \u03b1-galactosidase A: First example of a multivalent enzyme activity enhancer for Fabry disease","volume":"192","author":"Carmona","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"64847","DOI":"10.1039\/C6RA15806D","article-title":"Evidence for a multivalent effect in inhibition of sulfatases involved in lysosomal storage disorders (LSDs)","volume":"6","author":"Matassini","year":"2016","journal-title":"RSC Adv."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Matassini, C., D\u2019Adamio, G., Vanni, C., and Goti, A.F. (2019). Cardona Studies for the Multimerization of DAB-1-Based Iminosugars through Iteration of the Nitrone Cycloaddition\/Ring-Opening\/Allylation Sequence. Eur. J. Org. Chem., 4897\u20134905.","DOI":"10.1002\/ejoc.201900823"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8604","DOI":"10.1039\/C8OB02587H","article-title":"Multimerization of DAB-1 onto Au GNPs affords new potent and selective N-acetylgalactosamine-6-sulfatase (GALNS) inhibitors","volume":"16","author":"Matassini","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9362","DOI":"10.1039\/D3OB01466E","article-title":"Gold nanoparticles decorated with monosaccharides and sulfated ligands as potential modulators of the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS)","volume":"21","author":"Buco","year":"2023","journal-title":"Org. Biomol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1002\/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5","article-title":"Click Chemistry: Diverse Chemical Function from a few Good Reactions","volume":"40","author":"Kolb","year":"2001","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2596","DOI":"10.1002\/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4","article-title":"A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective \u201cLigation\u201d of Azides and Terminal Alkynes","volume":"41","author":"Rostovtsev","year":"2002","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1021\/jo011148j","article-title":"Peptidotriazoles on Solid Phase: [1,2,3]-Triazoles by Regiospecific Copper(I)-Catalyzed 1,3-Dipolar Cycloadditions of Terminal Alkynes to Azides","volume":"67","author":"Christensen","year":"2002","journal-title":"J. Org. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6250","DOI":"10.1039\/C4OB01117A","article-title":"6-Azido hyacinthacine A2 gives a straightforward access to the first multivalent pyrrolizidine architectures","volume":"12","author":"Parmeggiani","year":"2014","journal-title":"Org. Biomol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1021\/jo8008935","article-title":"Expeditive Synthesis of Glycodendrimer Scaffolds Based on Versatile TRIS and Mannoside Derivatives","volume":"73","author":"Chabre","year":"2008","journal-title":"J. Org. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Segura, M., Sansone, F., Casnati, A., and Ungaro, R. (2001). Synthesis of Lower Rim Polyhydroxylated Calix [4]arenes. Synthesis, 2105\u20132112.","DOI":"10.1055\/s-2001-18065"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mourer, M., Hapiot, F., Tilloy, S., Monflier, E., and Menuel, S. (2008). Easily Accessible Mono-and Polytopic \u03b2-Cyclodextrin Hosts by Click Chemistry. Eur. J. Org. Chem., 5723\u20135730.","DOI":"10.1002\/ejoc.200800728"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Papp, I., Dernedde, J., Enders, S., and Haag, R. (2008). Modular synthesis of multivalent glycoarchitectures and their unique selectin binding behavior. Chem. Commun., 5851\u20135853.","DOI":"10.1039\/b813414f"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Bail\u00e9n, M., Jim\u00e9nez-Ortega, E., Carmona, A.T., Robina, I., Sanz-Aparicio, J., Talens-Perales, D., Polaina, J., Matassini, C., Cardona, F., and Moreno-Vargas, A.J. (2019). Structural basis of the inhibition of GH1 \u03b2-glucosidases by multivalent pyrrolidine iminosugars. Bioorg. Chem., 89.","DOI":"10.1016\/j.bioorg.2019.103026"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6545","DOI":"10.1002\/chem.201003402","article-title":"Combining glycomimetic and multivalent strategies toward designing potent bacterial lectin inhibitors","volume":"17","author":"Chabre","year":"2011","journal-title":"Chem. Eur. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"14585","DOI":"10.1002\/chem.201703011","article-title":"Mechanistic Insight into the Binding of Multivalent Pyrrolidines to \u03b1-Mannosidases","volume":"23","author":"Mirabella","year":"2017","journal-title":"Chem. Eur. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2631","DOI":"10.3762\/bjoc.11.282","article-title":"Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar","volume":"11","author":"Matassini","year":"2015","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/cbic.201300442","article-title":"A systematic investigation of iminosugar click clusters as pharmacological chaperones for the treatment of Gaucher disease","volume":"15","author":"Joosten","year":"2014","journal-title":"ChemBioChem"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1021\/ol8007759","article-title":"Novel Polyhydroxylated Cyclic Nitrones and N-Hydroxypyrrolidines through BCl3-Mediated Deprotection","volume":"10","author":"Desvergnes","year":"2008","journal-title":"Org. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.bioorg.2019.03.053","article-title":"Dual targeting of PTP1B and glucosidases with new bifunctional iminosugar inhibitors to address type 2 diabetes","volume":"87","author":"Ferhati","year":"2019","journal-title":"Bioorg. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5186","DOI":"10.1002\/chem.200900076","article-title":"Controlling the Chair Conformation of a Mannopyranose in a Large-Amplitude [2] Rotaxane Molecular Machine","volume":"15","author":"Coutrot","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115105","DOI":"10.1016\/j.carbpol.2019.115105","article-title":"Synthesis of \u03b2-1,3-glucan mimics by \u03b2-1,3-glucan trisaccharyl monomer polymerization","volume":"227","author":"Miyagawa","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7591","DOI":"10.1039\/C6RA27181B","article-title":"Carbohydrates as potentially versatile core subcarriers for multivalent immunogens","volume":"7","author":"Kushwaha","year":"2017","journal-title":"RSC Adv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bmc.2009.10.060","article-title":"Nanomolar affinity, iminosugar-based chemical probes for specific labeling of lysosomal glucocerebrosidase","volume":"18","author":"Liskamp","year":"2010","journal-title":"Bioorg. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1002\/pola.29205","article-title":"Nonmigratory Internal Plasticization of Poly(Vinyl Chloride) via Pendant Triazoles Bearing Alkyl or Polyether Esters","volume":"56","author":"Higa","year":"2018","journal-title":"J. Polym. Sci. Part A Polym. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Matassini, C., Mirabella, S., Xhenti, F., Faggi, C., Robina, I., Goti, A., Moreno-Clavijo, E., Moreno-Vargas, A.J., and Cardona, F. (2014). Polyhydroxyamino-Piperidine-Type Iminosugars and Pipecolic Acid Analogues from a D-Mannose-Derived Aldehyde. Eur. J. Org. Chem., 5419\u20135432.","DOI":"10.1002\/ejoc.201402427"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e202200077","DOI":"10.1002\/cbic.202200077","article-title":"3,4,5-Trihydroxypiperidine Based Multivalent Glucocerebrosidase (GCase) Enhancers","volume":"23","author":"Vanni","year":"2022","journal-title":"ChemBioChem"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6740","DOI":"10.1016\/j.tetlet.2013.09.137","article-title":"Aniline\u2013terephthalaldehyde resin p-toluenesulfonic acid (ATRT) salt as efficient mild polymeric solid acid catalyst","volume":"54","author":"Tanemura","year":"2013","journal-title":"Tetrahedron Letters"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jinorgbio.2003.10.001","article-title":"A formula for correlating pKa values determined in D2O and H2O","volume":"98","author":"Bal","year":"2004","journal-title":"J. Inorg. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7512","DOI":"10.1021\/jo971176v","article-title":"NMR Chemical Shifts of Common Laboratory Solvents as Trace Impurities","volume":"62","author":"Gottlieb","year":"1997","journal-title":"Org. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4319","DOI":"10.1021\/jo4003135","article-title":"High-yield total synthesis of (-)-strictinin through intramolecular coupling of gallates","volume":"78","author":"Michihata","year":"2013","journal-title":"J. Org. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/10\/2222\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:35:47Z","timestamp":1760031347000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/10\/2222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":66,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["molecules30102222"],"URL":"https:\/\/doi.org\/10.3390\/molecules30102222","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,20]]}}}