{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T03:04:27Z","timestamp":1777431867212,"version":"3.51.4"},"reference-count":93,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,15]],"date-time":"2020-11-15T00:00:00Z","timestamp":1605398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Peptidoglycan (PGN) is a major constituent of most bacterial cell walls that is recognized as a primary target of the innate immune system. The availability of pure PGN molecules has become key to different biological studies. This review aims to (1) provide an overview of PGN biosynthesis, focusing on the main biosynthetic intermediates; (2) focus on the challenges for chemical synthesis posed by the unique and complex structure of PGN; and (3) cover the synthetic routes of PGN fragments developed to date. The key difficulties in the synthesis of PGN molecules mainly involve stereoselective glycosylation involving NAG derivatives. The complex synthesis of the carbohydrate backbone commonly involves multistep sequences of chemical reactions to install the lactyl moiety at the O-3 position of NAG derivatives and to control enantioselective glycosylation. Recent advances are presented and synthetic routes are described according to the main strategy used: (i) based on the availability of starting materials such as glucosamine derivatives; (ii) based on a particular orthogonal synthesis; and (iii) based on the use of other natural biopolymers as raw materials.<\/jats:p>","DOI":"10.3390\/ph13110392","type":"journal-article","created":{"date-parts":[[2020,11,16]],"date-time":"2020-11-16T11:04:20Z","timestamp":1605524660000},"page":"392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Assembly of Peptidoglycan Fragments\u2014A Synthetic Challenge"],"prefix":"10.3390","volume":"13","author":[{"given":"Fausto","family":"Queda","sequence":"first","affiliation":[{"name":"LAQV@REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"}]},{"given":"Gon\u00e7alo","family":"Covas","sequence":"additional","affiliation":[{"name":"UCIBIO@REQUIMTE, Departamento de Ci\u00eancias da Vida, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"},{"name":"Laboratory of Bacterial Cell Surfaces and Pathogenesis, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-832X","authenticated-orcid":false,"given":"S\u00e9rgio","family":"Filipe","sequence":"additional","affiliation":[{"name":"UCIBIO@REQUIMTE, Departamento de Ci\u00eancias da Vida, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"},{"name":"Laboratory of Bacterial Cell Surfaces and Pathogenesis, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-752X","authenticated-orcid":false,"given":"M.","family":"Marques","sequence":"additional","affiliation":[{"name":"LAQV@REQUIMTE, Departamento de Qu\u00edmica, Faculdade de Ci\u00eancias e Tecnologia, Universidade Nova de Lisboa, Campus de Caparica, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1128\/br.36.4.407-477.1972","article-title":"Peptidoglycan types of bacterial cell-walls and their taxonomic implications","volume":"36","author":"Schleifer","year":"1972","journal-title":"Bacteriol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1128\/MMBR.62.1.181-203.1998","article-title":"Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli","volume":"62","author":"Holtje","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.mib.2013.06.012","article-title":"Auxiliary factors: A chink in the armor of MRSA resistance to beta-lactam antibiotics","volume":"16","author":"Roemer","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1086\/491711","article-title":"Vancomycin resistance in gram-positive cocci","volume":"42","author":"Courvalin","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/nrmicro2333","article-title":"How antibiotics kill bacteria: From targets to networks","volume":"8","author":"Kohanski","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1574-6976.2007.00099.x","article-title":"Bacterial peptidoglycan (murein) hydrolases","volume":"32","author":"Vollmer","year":"2008","journal-title":"Fems Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.cell.2014.11.017","article-title":"Beta-Lactam Antibiotics Induce a Lethal Malfunctioning of the Bacterial Cell Wall Synthesis Machinery","volume":"159","author":"Cho","year":"2014","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/1574-6976.12006","article-title":"Diversity in bacterial lysis systems: Bacteriophages show the way","volume":"37","author":"Catalao","year":"2013","journal-title":"Fems Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1038\/sj.emboj.7601363","article-title":"Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and present peptidoglycan to PGRP-SA","volume":"25","author":"Wang","year":"2006","journal-title":"Embo J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.tet.2013.11.064","article-title":"Recent advances in the synthesis of chitooligosaccharides and congeners","volume":"70","author":"Yang","year":"2014","journal-title":"Tetrahedron"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1002\/cbic.201000561","article-title":"Synthesis, Evaluation, and Mechanism of N,N,N-Trimethyl-D-glucosamine-(1 -> 4)-chitooligosaccharides as Selective Inhibitors of Glycosyl Hydrolase Family 20 beta-N-Acetyl-D-hexosaminidases","volume":"12","author":"Yang","year":"2011","journal-title":"Chembiochem"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1021\/ol201806d","article-title":"A New Synthetic Approach toward Bacterial Transglycosylase Substrates, Lipid II and Lipid IV","volume":"13","author":"Shih","year":"2011","journal-title":"Org. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7802","DOI":"10.1039\/C7OB01201B","article-title":"Synthesis of lipo-chitooligosaccharide analogues and their interaction with LYR3, a high affinity binding protein for Nod factors and Myc-LCOs","volume":"15","author":"Berthelot","year":"2017","journal-title":"Org. Biomol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1002\/asia.201200338","article-title":"Stereoselective Glycosylation of Glucosamine: The Role of the N-Protecting Group","volume":"7","author":"Enugala","year":"2012","journal-title":"Chem. Asian J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.carres.2006.10.021","article-title":"Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars","volume":"342","author":"Bongat","year":"2007","journal-title":"Carbohydr. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2245","DOI":"10.1002\/anie.200461988","article-title":"Direct and stereoselective synthesis of 2-acetamido-2-deoxy-beta-D-glycopyranosides by using the phosphite method","volume":"44","author":"Arihara","year":"2005","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1002\/ejoc.201200062","article-title":"Highly Selective Formation of beta-Glycosides of N-Acetylglucosamine Using Catalytic Iron(III) Triflate","volume":"2012","author":"Stevenin","year":"2012","journal-title":"Eur. J. Org. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6819","DOI":"10.1021\/ja010086b","article-title":"Why are the hydroxy groups of partially protected N-acetylglucosamine derivatives such poor glycosyl accepters, and what can be done about it? A comparative study of the reactivity of N-acetyl-, N-phthalimido-, and 2-azido-2-deoxy-glucosamine derivatives in glycosylation. 2-picolinyl ethers as reactivity-enhancing replacements for benzyl ethers","volume":"123","author":"Crich","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1021\/bi00407a006","article-title":"Glucosamine synthetase from escherichia-coli kinetic mechanism and inhibition by n3-fumaroyl-l-2,3-diaminopropionic derivatives","volume":"27","author":"Badet","year":"1988","journal-title":"Biochemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/0003-9861(92)90018-R","article-title":"Chemical modification of glucosamine-6-phosphate synthase by diethyl pyrocarbonate\u2014Evidence of histidine requirement for enzymatic-activity","volume":"292","author":"Badetdenisot","year":"1992","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1021\/bi952275a","article-title":"Acetyltransfer precedes uridylyltransfer in the formation of UDP-N-acetylglucosamine in separable active sites of the bifunctional GlmU protein of Escherichia coli","volume":"35","author":"Gehring","year":"1996","journal-title":"Biochemistry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1046\/j.1432-1327.1999.00373.x","article-title":"Reaction mechanism of phosphoglucosamine mutase from Escherichia coli","volume":"262","author":"Jolly","year":"1999","journal-title":"Eur. J. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5788","DOI":"10.1128\/jb.176.18.5788-5795.1994","article-title":"Copurification of glucosamine-1-phosphate acetyltransferase and n-acetylglucosamine-1-phosphate uridyltransferase activities of escherichia-coli-characterization of the glmu gene-product as a bifunctional enzyme catalyzing 2 subsequent steps in the pathway for udp-n-acetylglucosamine synthesis","volume":"176","author":"Menginlecreulx","year":"1994","journal-title":"J. Bacteriol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1074\/jbc.271.1.32","article-title":"Characterization of the essential gene glmM encoding phosphoglucosamine mutase in Escherichia coli","volume":"271","author":"MenginLecreulx","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1021\/bi00059a019","article-title":"Overexpression, purification, and mechanistic study of udp-n-acetylenolpyruvylglucosamine reductase","volume":"32","author":"Benson","year":"1993","journal-title":"Biochemistry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1021\/bi962220o","article-title":"Kinetic characterization of wild-type and S229A mutant MurB: Evidence for the role of ser 229 as a general acid","volume":"36","author":"Benson","year":"1997","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12671","DOI":"10.1021\/bi001310x","article-title":"Determination of the pK(a) value of C115 in MurA (UDP-N-acetylglucosamine enolpyruvyltransferase) from Enterobacter cloacae","volume":"39","author":"Krekel","year":"2000","journal-title":"Biochemistry"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1128\/jb.175.10.2970-2979.1993","article-title":"The muri gene of escherichia-coli is an essential gene that encodes a glutamate racemase activity","volume":"175","author":"Doublet","year":"1993","journal-title":"J. Bacteriol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.1021\/bi00183a035","article-title":"The glutamate racemase activity from escherichia-coli is regulated by peptidoglycan precursor udp-n-acetylmuramoyl-l-alanine","volume":"33","author":"Doublet","year":"1994","journal-title":"Biochemistry"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1107\/S0907444911050682","article-title":"Structural features and kinetic characterization of alanine racemase from Staphylococcus aureus (Mu50)","volume":"68","author":"Scaletti","year":"2012","journal-title":"Acta Crystallogr. Sect. D Struct. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/mmi.12758","article-title":"The biology of Mur ligases as an antibacterial target","volume":"94","author":"Kouidmi","year":"2014","journal-title":"Mol. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"33439","DOI":"10.1074\/jbc.M113.508135","article-title":"Specificity Determinants for Lysine Incorporation in Staphylococcus aureus Peptidoglycan as Revealed by the Structure of a MurE Enzyme Ternary Complex","volume":"288","author":"Ruane","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1006\/jmbi.1999.2800","article-title":"Determination of the MurD mechanism through crystallographic analysis of enzyme complexes","volume":"289","author":"Bertrand","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1002\/pro.5560051219","article-title":"Kinetic and crystallographic studies of Escherichia coli UDP-N-acetylmuramate: L-alanine ligase","volume":"5","author":"Emanuele","year":"1996","journal-title":"Protein Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1021\/bi00220a033","article-title":"Existence of 2 d-alanine-d-alanine ligases in escherichia-coli-cloning and sequencing of the ddla gene and purification and characterization of the ddla and ddlb enzymes","volume":"30","author":"Zawadzke","year":"1991","journal-title":"Biochemistry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"16264","DOI":"10.1021\/bi961872+","article-title":"Kinetic mechanism of the Escherichia coli UDPMurNAc-tripeptide D-alanyl-D-alanine-adding enzyme: Use of a glutathione S-transferase fusion","volume":"35","author":"Anderson","year":"1996","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1042\/bj2820747","article-title":"D-alanine-d-alanine ligase of escherichia-coli-expression, purification and inhibitory studies on the cloned enzyme","volume":"282","author":"Albar","year":"1992","journal-title":"Biochem. J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8919","DOI":"10.1021\/bi8006274","article-title":"Active site mapping of MraY, a member of the polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase superfamily, catalyzing the first membrane step of peptidoglycan biosynthesis","volume":"47","author":"Henry","year":"2008","journal-title":"Biochemistry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1126\/science.1236501","article-title":"Crystal Structure of MraY, an Essential Membrane Enzyme for Bacterial Cell Wall Synthesis","volume":"341","author":"Chung","year":"2013","journal-title":"Science"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29974","DOI":"10.1074\/jbc.M314165200","article-title":"Purification and characterization of the bacterial MraY translocase catalyzing the first membrane step of peptidoglycan biosynthesis","volume":"279","author":"Bouhss","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1073\/pnas.53.4.881","article-title":"Lipid-phosphoacetylmuramyl-pentapeptide and lipid-phosphodisaccharide-pentapeptide\u2013presumed membrane transport intermediates in cell wall synthesis","volume":"53","author":"Anderson","year":"1965","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1128\/MMBR.00016-07","article-title":"Lipid intermediates in the biosynthesis of bacterial peptidoglycan","volume":"71","year":"2007","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4625","DOI":"10.1128\/jb.173.15.4625-4636.1991","article-title":"The murg gene of escherichia-coli codes for the udp-n-acetylglucosamine-n-acetylmuramyl-(pentapeptide) pyrophosphoryl-undecaprenol n-acetylglucosamine transferase involved in the membrane steps of peptidoglycan synthesis","volume":"173","author":"Menginlecreulx","year":"1991","journal-title":"J. Bacteriol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/emboj.2011.61","article-title":"Identification of FtsW as a transporter of lipid-linked cell wall precursors across the membrane","volume":"30","author":"Mohammadi","year":"2011","journal-title":"Embo J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"15553","DOI":"10.1073\/pnas.0808352105","article-title":"Bioinformatics identification of MurJ (MviN) as the peptidoglycan lipid II flippase in Escherichia coli","volume":"105","author":"Ruiz","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1126\/science.1254522","article-title":"MurJ is the flippase of lipid-linked precursors for peptidoglycan biogenesis","volume":"345","author":"Sham","year":"2014","journal-title":"Science"},{"key":"ref_47","first-page":"21","article-title":"Lipid Flippases for Bacterial Peptidoglycan Biosynthesis","volume":"8","author":"Ruiz","year":"2015","journal-title":"Lipid Insights"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"495","DOI":"10.3390\/antibiotics4040495","article-title":"Core Steps of Membrane-Bound Peptidoglycan Biosynthesis: Recent Advances, Insight and Opportunities","volume":"4","author":"Teo","year":"2015","journal-title":"Antibiot. Basel"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1073\/pnas.1504967112","article-title":"MurJ and a novel lipid II flippase are required for cell wall biogenesis in Bacillus subtilis","volume":"112","author":"Meeske","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/s41579-020-0366-3","article-title":"Regulation of peptidoglycan synthesis and remodelling","volume":"18","author":"Egan","year":"2020","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1089\/mdr.2014.0035","article-title":"Deciphering the metabolism of undecaprenyl-phosphate: The bacterial cell-wall unit carrier at the membrane frontier","volume":"20","author":"Manat","year":"2014","journal-title":"Microb. Drug Resist."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"10874","DOI":"10.1021\/ja505668f","article-title":"Reconstitution of Peptidoglycan Cross-Linking Leads to Improved Fluorescent Probes of Cell Wall Synthesis","volume":"136","author":"Lebar","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1038\/sj.embor.7400248","article-title":"Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition","volume":"5","author":"Travassos","year":"2004","journal-title":"EMBO Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nri.2017.136","article-title":"Peptidoglycan recognition by the innate immune system","volume":"18","author":"Wolf","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7613","DOI":"10.1016\/S0040-4039(01)01619-7","article-title":"Synthetic study of peptidoglycan partial structures. Synthesis of tetrasaccharide and octasaccharide fragments","volume":"42","author":"Inamura","year":"2001","journal-title":"Tetrahedron Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1246\/bcsj.59.1411","article-title":"Chemical synthesis and biological-activities of 2 disaccharide dipeptides corresponding to the repeating units of bacterial peptidoglycan","volume":"59","author":"Kusumoto","year":"1986","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"11638","DOI":"10.1021\/ja0166848","article-title":"Lipid II: Total synthesis of the bacterial cell wall precursor and utilization as a substrate for glycosyltransfer and transpeptidation by penicillin binding protein (PBP) 1b of Eschericia coli","volume":"123","author":"Schwartz","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3575","DOI":"10.1021\/ol016692t","article-title":"Synthesis of an orthogonally protected precursor to the glycan repeating unit of the bacterial cell wall","volume":"3","author":"Saha","year":"2001","journal-title":"Org. Lett."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1021\/ja017386d","article-title":"The first total synthesis of lipid II: The final monomeric intermediate in bacterial cell wall biosynthesis","volume":"124","author":"VanNieuwenhze","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7805","DOI":"10.1016\/S0040-4039(02)01753-7","article-title":"A highly convergent approach for the synthesis of disaccharide repeating units of peptidoglycan","volume":"43","author":"Chowdhury","year":"2002","journal-title":"Tetrahedron Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1021\/jo035583k","article-title":"Synthesis of a fragment of bacterial cell wall","volume":"69","author":"Hesek","year":"2004","journal-title":"J. Org. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1039\/B511866B","article-title":"Synthesis of peptidoglycan fragments and evaluation of their biological activity","volume":"4","author":"Inamura","year":"2006","journal-title":"Org. Biomol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1021\/ja069060g","article-title":"Synthesis of heptaprenyl-lipid IV to analyze peptidoglycan glycosyltransferases","volume":"129","author":"Zhang","year":"2007","journal-title":"J. Am. Chem. Soc."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.1021\/ja010028q","article-title":"Better substrates for bacterial transglycosylases","volume":"123","author":"Ye","year":"2001","journal-title":"J. Am. Chem. Soc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3631","DOI":"10.1016\/j.tetlet.2009.03.081","article-title":"Synthesis of crosslinked peptidoglycan fragments for investigation of their immunobiological functions","volume":"50","author":"Fujimoto","year":"2009","journal-title":"Tetrahedron Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1462-5822.2004.00433.x","article-title":"Muramyldipeptide and diaminopimelic acid-containing desmuramylpeptides in combination with chemically synthesized Toll-like receptor agonists synergistically induced production of interleukin-8 in a NOD2- and NOD1-dependent manner, respectively, in human monocytic cells in culture","volume":"7","author":"Uehara","year":"2005","journal-title":"Cell. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1002\/cbic.201200655","article-title":"Glycan Sequence-Dependent Nod2 Activation Investigated by Using a Chemically Synthesized Bacterial Peptidoglycan Fragment Library","volume":"14","author":"Wang","year":"2013","journal-title":"Chembiochem"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1039\/c2np00091a","article-title":"Peptidoglycan as Nod1 ligand; fragment structures in the environment, chemical synthesis, and their innate immunostimulation","volume":"29","author":"Fujimoto","year":"2012","journal-title":"Nat. Prod. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1177\/0968051907080739","article-title":"Chemical synthesis of peptidoglycan fragments for elucidation of the immunostimulating mechanism","volume":"13","author":"Fujimoto","year":"2007","journal-title":"J. Endotoxin Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.carres.2013.12.007","article-title":"Synthesis of the NAG-NAM disaccharide via a versatile intermediate","volume":"384","author":"Enugala","year":"2014","journal-title":"Carbohydr. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1039\/C5OB02145F","article-title":"Synthesis of characteristic Mycobacterium peptidoglycan (PGN) fragments utilizing with chemoenzymatic preparation of meso-diaminopimelic acid (DAP), and their modulation of innate immune responses","volume":"14","author":"Wang","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Enugala, R., and Marques, M.M.B. (2012). Synthesis of a 3-hydroxyl-free N-acetyl glucosamine disaccharide. Arkivoc, 90\u2013100.","DOI":"10.3998\/ark.5550190.0013.608"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1021\/acs.joc.6b02305","article-title":"Why Is Direct Glycosylation with N-Acetylglucosamine Donors Such a Poor Reaction and What Can Be Done about It?","volume":"82","author":"Marqvorsen","year":"2017","journal-title":"J. Org. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1039\/C4QO00183D","article-title":"Glycosylation with N-acetyl glycosamine donors using catalytic iron(III) triflate: From microwave batch chemistry to a scalable continuous-flow process","volume":"1","author":"Xolin","year":"2014","journal-title":"Org. Chem. Front."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Enugala, R., Carvalho, L.C.R., and Marques, M.M.B. (2010). Towards Glucosamine Building Blocks: Regioselective One-Pot Protection and Deallylation Procedures. Synlett, 2711\u20132716.","DOI":"10.1055\/s-0030-1259001"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1002\/mrc.2583","article-title":"Application of HR-MAS NMR in the solid-phase synthesis of a glycopeptide using Sieber amide resin","volume":"48","author":"Carvalho","year":"2010","journal-title":"Magn. Reson. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8025","DOI":"10.1021\/acs.chemrev.8b00036","article-title":"\u201cOne-Pot\u201d Protection, Glycosylation, and Protection-Glycosylation Strategies of Carbohydrates","volume":"118","author":"Kulkarni","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2510","DOI":"10.1002\/anie.199625101","article-title":"Orthogonal glycosylation strategy for rapid assembly of oligosaccharides on a polymer support","volume":"35","author":"Ito","year":"1996","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1002\/ajoc.201800592","article-title":"From a Natural Polymer to Relevant NAG-NAM Precursors","volume":"7","author":"Carvalho","year":"2018","journal-title":"Asian J. Org. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0008-6215(89)85021-9","article-title":"Peracetylated chitobiose-preparation by specific degradations of chitin, and chemical manipulations","volume":"194","author":"Nishimura","year":"1989","journal-title":"Carbohydr. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1039\/b208953j","article-title":"Probing the mechanism of a fungal glycosyltransferase essential for cell wall biosynthesis. UDP-chitobiose is not a substrate for chitin synthase","volume":"1","author":"Chang","year":"2003","journal-title":"Org. Biomol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"11912","DOI":"10.1002\/anie.201406802","article-title":"From Chitin to Bioactive Chitooligosaccharides and Conjugates: Access to Lipochitooligosaccharides and the TMG-chitotriomycin","volume":"53","author":"Despras","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Queda, F., Covas, G., Silva, T., Santos, C.A., Bronze, M.R., Canada, F.J., Corvo, M.C., Filipe, S.R., and Marques, M.M.B. (2019). A top-down chemo-enzymatic approach towards N-acetylglucosamine-N-acetylmuramic oligosaccharides: Chitosan as a reliable template. Carbohydr. Polym., 224.","DOI":"10.1016\/j.carbpol.2019.115133"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1128\/jb.146.2.755-763.1981","article-title":"Peptidoglycan loss during hen egg-white lysozyme-inorganic salt lysis of streptococcus-mutans","volume":"146","author":"Goodman","year":"1981","journal-title":"J. Bacteriol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/bm0101163","article-title":"Chemoselective protection of the amino groups of chitosan by controlled phthaloylation: Facile preparation of a precursor useful for chemical modifications","volume":"3","author":"Kurita","year":"2002","journal-title":"Biomacromolecules"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1021\/bm0610976","article-title":"Regioselective silylation of N-phthaloylchitosan with TBDMS and TBDPS groups","volume":"8","author":"Binette","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"12604","DOI":"10.1021\/ja407445x","article-title":"Cell-Wall Remodeling by the Zinc-Protease AmpDh3 from Pseudomonas aeruginosa","volume":"135","author":"Lee","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/35090602","article-title":"Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate","volume":"412","author":"Vocadlo","year":"2001","journal-title":"Nature"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S0922-338X(97)82012-0","article-title":"Enzymatic hydrolysis reaction of water-soluble chitin derivatives with egg white lysozyme","volume":"84","author":"Maeda","year":"1997","journal-title":"J. Ferment. Bioeng."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/j.1432-1033.1978.tb12216.x","article-title":"Action of lysozyme on partially deacetylated chitin","volume":"85","author":"Amano","year":"1978","journal-title":"Eur. J. Biochem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S0378-1097(03)00793-6","article-title":"A method for the enzymatic synthesis and HPLC purification of the peptidoglycan precursor UDP-N-acetylmuramic acid","volume":"229","author":"Raymond","year":"2003","journal-title":"Fems Microbiol. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"8060","DOI":"10.1002\/anie.201402313","article-title":"Enzymatic Synthesis of Lipid II and Analogues","volume":"53","author":"Huang","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.carres.2017.04.005","article-title":"Enzymatic synthesis and semi-preparative isolation of N-acetylmuramic acid 6-phosphate","volume":"445","author":"Unsleber","year":"2017","journal-title":"Carbohydr. Res."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/11\/392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:33:36Z","timestamp":1760178816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/11\/392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,15]]},"references-count":93,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ph13110392"],"URL":"https:\/\/doi.org\/10.3390\/ph13110392","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,15]]}}}