DOCSLIB.ORG

Programmable One-Pot Synthesis of Heparin Pentasaccharide Fondaparinux Supriya Dey†, Hong-Jay Lo†, Chi-Huey Wong*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Programmable One-Pot Synthesis of Heparin Pentasaccharide Fondaparinux Supriya Dey†, Hong-Jay Lo†, Chi-Huey Wong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`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iT,C,Cj+-/'%/18.+%#$+ /01+$(::(2)9/.+(#+/01+'18("7+%#$+-/1'1"-1912/(;1+89.2"-.9%/("#+ $1-(8#1$+/0("89.2"-($1-+<),+!*+%#$+!+@+%-+4)(9$(#8+49"2N-E++ 41/311#+/01+89)2"-%5(#1,+89)2)'"#(2+%2($+%#$+($)'"#(2+%2($+ 699+/01+4)(9$(#8+49"2N-+%'1+'1%$(9.+%//%(#%491+:'"5+2"57 4)(9$(#8+49"2N-+%#$+/01+-/'%/18(2+(#-/%99%/("#+":+XQX#&+%#$+ 51'2(%99.+%;%(9%491+5"#"-%220%'($1-E+?01+-.#/01/(2+$1-(8#+ PFQX#&+8'")&-E+K#+&%'/(2)9%',+/01+T,C7!"#+"'+S789.2"-.9%/("#+ (#;"9;1-+/01+)-1+":+")'+1-/%49(-01$+&'"8'%55%491+"#17&"/+ 41/311#+%+89)2"-%5(#1+%#$+%#+)'"#(2+%2($+4)(9$(#8+49"2N+ 51/0"$+ /"+ 2"#$)2/+ 0(809.+ S7-1912/(;1+ 89.2"-.9%/("#+ )-(#8+ 3(/0")/+/01+:"'5%/("#+":+/01+)#3%#/1$+V7(-"51'+%-+3199+%-+ ?f=AQ+%#$+62+8'")&-+%/+XR+%#$+9%/1+-/%81+(#/'"$)2/("#+":+ (5&'";151#/+":+/01+";1'%99+.(19$+(#+%+-0"'/1-/+&"--(491+-.#7 /01+%2($(2+:)#2/("#%9(/(1-+<89)2)'"#(2+%#$+K$)'"#(2@E+!"'+/01+ /01/(2+'")/1+'1&'1-1#/-+%+5%J"'+20%991#81E+K#+/01+&%-/+.1%'-,+ -1912/(;1+(#-/%99%/("#+":+/01+W7QX#&-8'")&,+31+5%-N1$+/01+eW7 5%#.+8'")&-,+(#29)$(#8+/0%/+":+A1/(/"),'+I(#,(+F)#8,)+H%#8,*+ 0.$'"*.9+ 8'")&+ <eW7XF@+ 3(/0+ %#+ "'/0"8"#%9+ &'"/12/(#8+ a(#,!++G%#(N"3-N(,!!%#$+=(#8!"+0%;1+'1&"'/1$+/01+-.#/01-(-+ 8'")&,+#%519.,+C7#%&/0.9+1/01'+<P%&@E++?01+-.#/01-(-+":+C7 ":+!"#$%&%'(#)*,+4)/+/01+&'"21$)'1-+-/(99+1#2")#/1'+&'"47 %h($"+/0("89.2"-($1+$"#"'+)+3%-+%20(1;1$+:'"5+!789)2"-%7 915-+":+9"#8+-/1&3(-1+&'"21--,+#"#7-/1'1"-1912/(;1+89.2"-.97 5(#1+0.$'"209"'($1+)-(#8+")'+&'1;(")-+'1&"'/1$+&'"21$)'1+ %/("#+%#$+9"3+.(19$+%#$+1::(2(1#2.E+b0%"+%#$+2"73"'N1'-+'17 <Q)&&"'/(#8+ K#:"'5%/("#,+ Q20151+ QT@E!'/- ?01+ dd>-+ ":+ /01+ 21#/9.+ '1&"'/1$+ %+ &'17%2/(;%/("#+ 4%-1$+ (/1'%/(;1+ "#17&"/+ #139.+-.#/01-(h1$+4)(9$(#8+49"2N-+31'1+51%-)'1$+4.+FAIe+ -.#/01-(-+":+!"#$%&%'(#)*+3(/0+91--+/0%#+UDc+.(19$E!#+H1+ %#%9.-(-+(#+%+2"5&1/(/("#+%--%.+3(/0+%+'1:1'1#21+/0("89.2"7 /0")80/+/01+51/0"$+":+&'"8'%55%491+"#17&"/+-.#/01-(-+":+ -($1+$"#"'+":+N#"3#+dd>+<Q)&&"'/(#8+K#:"'5%/("#@E!$,!%- "9(8"-%220%'($1-+ )-(#8+ $1-(8#1$+ /0("89.2"-($1+ 4)(9$(#8+ ?01+-.#/01-(-+":+$(-%220%'($1+!*+(#;"9;1$+/01+89.2"-.9%7 49"2N-+3(/0+$1:(#1$+'19%/(;1+'1%2/(;(/.+;%9)1-+<dd>-@+$1;197 /("#+41/311#+89.2"-.9+/'(209"'"%21/(5($%/1+,!(-%#$+/0("89.7 "&1$+4.+)-!$,-!%+2")9$+41+)-1:)9+:"'+/01+&'%2/(2%9+-.#/01-(-+":+ 2"-($1+%221&/"'+-!)-(#+/01+&'1-1#21+":+?GQX?:+/"+81#1'%/1+.+ !E(++ (#+gRc+.(19$E+bk5&91#+$17%21/.9%/("#+8%;1+/+%#$+'741#h.9%7 ?01+2"#21&/+":+dd>+(-+4%-1$+"#+/01+M)%#/(/%/(;1+$1/1'5(7 /("#+":+Cl,Wl7XF+91$+/"+/01+:"'5%/("#+":+0+(#+[Dc+.(19$E+d17 #%/("#+":+/01+'1%2/(;(/.+":+%+/0("89.2"-($1+$"#"'+3(/0+51/07 5";%9+":+/01+C7P%&+&'"/12/(#8+8'")&+)-(#8+==a!*+:)'#(-01$+ %#"9+%-+2"5&%'1$+/"+/01+'1%2/(;(/.+":+/01+/0("89.2"-($1+$"7 $(-%220%'($1++(3(/0+:'11+0.$'"*.9+8'")&+%/+eW+(#+[Uc+.(19$E+ #"'+":+$%&7%21/.9+5%##"-1E+dd>+(-+51%-)'1$+)-(#8+FAIe+/"+ d15";%9+":+/01+-(9.9+&'"/12/(#8+8'")&+)#$1'+!&+-")'21+<F!7 $1/1'5(#1+ /01+ %5")#/+ ":+ 91%;(#8+ 8'")&+ '191%-1$+ %#$+ /01+ A.@+:"99"31$+4.+&'"/12/("#+":+W,R7XF+%-+%21/.9+1-/1'+)-(#8+ -/%'/(#8+$"#"'+91:/+(#+/01+'1%2/("#+/(51+2")'-1E+H(/0+/01+dd>+ 62"X^&.+91$+/"+1+(#+gDc+.(19$E+F.$'"9.-(-+":+/01+Ul,Rl7X741#7 ":+ ;%'(")-+ /0("89.2"-($1+ 4)(9$(#8+ 49"2N-+ <ffI-@+ %;%(9%491,+ h.9($1#1+%21/%9+)-(#8+[D+c+62XF7F"X+&'"$)21$+/01+2')$1+ "#1+2%#+$1-(8#+%+2"5&)/1'+-":/3%'1+/"+8)($1+/01+-1912/("#+ $(0.$'"*.+$1'(;%/(;1+:"'+/01+-1912/(;1+"*($%/("#+":+/01+&'(7 ":+%&&'"&'(%/1+ffI-+3(/0+31997$(::1'1#/(%/1$+dd>-+:"'+/01+ 5%'.+0.$'"*.9+8'")&+/"+2%'4"*.9(2+%2($+)-(#8+?BGAX^f6Kf+ "#17&"/+ %--1549.+ ":+ "9(8"-%220%'($1-E+ + H1+ $1;19"&1$+ /01+ %#$+-)4-1M)1#/+1-/1'(:(2%/("#+3(/0+G1K^mFeX#+/"+8(;1+$(7 :('-/+2"5&)/1'+&'"8'%5,+YX&/(51'Z+(#+Tggg!$-%-+%+$%/%4%-1+ -%220%'($1+%221&/"'+!*+(#+][+c+.(19$+<Q20151+T@E++ -1%'20+/""9+:"'+/01+'%&($+"#17&"/+%--1549.+":+9%'81+#)541'-+ Q20151+TE+Q.#/01-(-+":+!7O927V7<TnU@7!7O92P#+=(-%220%7 ":+9(#1%'+%#$+4'%#201$+2"5&91*+"9(8"-%220%'($1-+(#29)$(#8+ '($1+f)(9$(#8+f9"2N+ P789.2%#-!%+ %#$+ 89.2"-%5(#"89.2%#-E!'+ K#+ CDT[,+ 31+ '17 &"'/1$+%#+)&8'%$1$+;1'-("#+":+/0(-+-":/3%'1,+#%519.,+6)/"+ eFX+3(/0+%+9(4'%'.+":+T]D+4)(9$(#8+49"2N-+<ffI-@+3(/0+1*7 &1'(51#/%99.+ 51%-)'1$+ dd>-+ %#$+ ]D,DDD+ ffI-+ 3(/0+ &'17 $(2/1$+dd>-+4.+5%20(#1+91%'#(#8+<(#29)$(#8+/0"-1+3(/0+dd>+ &'1$(2/1$+4.+2015(2%9+-0(:/-+4.+PGd@!$+/"+$(;1'-(:.+/01+%&7 &9(2%4(9(/.+":+/01+-":/3%'1+:"'+/01+-.#/01-(-+":+"9(8"-%220%7 '($1-E++?"+)-1+1(/01'+YX&/(51'Z+"'+Y6)/"+eFXZ+-":/3%'1,+/01+ )-1'+ #11$-+ /"+ (#&)/+ /01+ $1-('1$+ "9(8"-%220%'($1+ -/')2/)'1+ + /01#+ /01+ -":/3%'1+ 3(99+ 81#1'%/1+ "#1+ "'+ 5"'1+ -.#/01/(2+ '")/1-+4%-1$+"#+/01+dd>-+":+/01+ffI-+#11$1$+:"'+/01+-.#7 /01-(-+ ":+ /01+ "9(8"-%220%'($1+ %-+ ")/&)/E+ X#21+ /01+ )-1'+ 20""-1-+%+-&12(:(2+-.#/01/(2+'")/1+:'"5+/01+")/&)/,+ffI-+%'1+ '1M)('1$+/"+41+-.#/01-(h1$+(#+/01+9%4"'%/"'.+%#$+/01#+"#17 &"/+ -.#/01-(-+ 2%#+ 41+ &1':"'51$+ 4.+ -1M)1#/(%9+ %$$(/("#+ ":+ ffI-+-/%'/(#8+:'"5+/01+5"-/+'1%2/(;1+:'"5+/01+#"#7'1$)2(#8+ 1#$+)#(/+/"3%'$+/01+91--+'1%2/(;1,+91%-/+'1%2/(;1+%#$+-"+"#+(#+ + /01+'1$)2(#8+1#$E+?01+"#17&"/+-/'%/18.+3%-+-)221--:)99.+%&7 !"'+ /01+ -.#/01-(-+ ":+ K$"7O92P#+ $(-%220%'($1+ $1'(;%/(;1-+ &9(1$+ /"+ /01+ -.#/01-(-+ ":+ 01&%'(#79(N1+ "9(8"-%220%'($1-!'.,/+ <!0+o+!+@,+31+)-1$+2"551'2(%99.+%;%(9%491+$(%21/"#1+89)7 %#$+/01+01&%'(#74%-1$+%#/(2"%8)9%#/+K$'%&%'(#)*E!'0+ 2"-1+!!(30(20+3%-+2"#;1'/1$+/"+S7"7($"&.'%#"-($1+!)()-(#8+ N#"3#+&'"21$)'1-E"++?01+C7XF+8'")&+":+!)(3%-+&'"/12/1$+ ?01+4)(9$(#8+49"2N-+)-1$+(#+/0(-+"#17&"/+-/'%/18.+%99"3+ 4"/0+%-+41#h".9+<fh@+%#$+%21/.9+1-/1'+<62@+/"+81#1'%/1+!,!'/+ $(::1'1#/(%9+'15";%9+":+/01+&'"/12/(#8+8'")&-+:"'+/01+'18(7 %#$+!-,+(#+[Dc+%#$+g]c+.(19$,+'1-&12/(;19.E+PKQ^?GQX?:7 "-1912/(;1+(#/'"$)2/("#+":+-)9:%/1+8'")&-+/"+1;%9)%/1+/01('+ G1$(%/1$+89.2"-.9%/("#+":+!,+3(/0+S751/0.9+%221&/"'+!1!'/+ 81#1'%/1$+$(-%220%'($1+!.+(#+gUc+.(19$E+?01+Up,Rp7'741#h.97 fh+&'"/12/1$+$(-%220%'($1+!0+<Q20151+W@+%#$+0(801'+.(19$+ ($1#1+%21/%9+3%-+0.$'"9.h1$+)-(#8+[Dc+62XF+%#$+/01+2')$1+ ":+)!+<]Dc@+)-(#8+C7X62+2"#/%(#(#8+$(-%220%'($1+!+E++ $(0.$'"*.+$1'(;%/(;1+3%-+/'1%/1$+3(/0+?BGAX^f6Kf+/"+"*7 + ($(h1+/01+&'(5%'.+0.$'"*.9+8'")&+/"+%2($+%#$+-)4-1M)1#/+1-7 Q20151+UE+Q.#/01-(-+":+!"#$%&%'(#)*++ /1'(:(2%/("#+ ":+ /01+ %2($+ 3(/0+ G1K^mFeX#+ 81#1'%/1$+ "7($)7 '"#(2+%2($72"#/%(#(#8+$(-%220%'($1+%221&/"'+!0+(#+][c+.(19$+ <Q20151+C@E+K/+(-+#"/1$+/0%/+31+0%;1+%9-"+'1&"'/1$+/01+-.#7 /01-(-+":+!0+)-(#8+%+$(::1'1#/+-.#/01/(2+'")/1E!'/+ + Q20151+CE+Q.#/01-(-+":+"7K$"7S7<TnU@7!7O92P#+=(-%220%7 '($1+f)(9$(#8+f9"2N+ + Q20151+WE+X#17&"/+Q.#/01-(-+":+A'"/12/1$+!"#$%&%'(#)*++
Load more

Recommended publications
  • Gem-Diamine 1-N-Iminosugars As Versatile Glycomimetics: Synthesis, Biological Activity and Therapeutic Potential
    The Journal of Antibiotics (2009) 62, 407–423 & 2009 Japan Antibiotics Research Association All rights reserved 0021-8820/09 $32.00 www.nature.com/ja REVIEW ARTICLE Gem-diamine 1-N-iminosugars as versatile glycomimetics: synthesis, biological activity and therapeutic potential Yoshio Nishimura Iminosugars, which carry a basic nitrogen in the carbohydrate ring, have attracted increasing interest as new glycomimetics. Gem-diamine 1-N-iminosugars, a new class of iminosugars, have a nitrogen atom in place of the anomeric carbon. Various kinds of 1-N-iminosugars have been synthesized from glyconolactones as a chiral source in a totally stereospecific manner and/or by the convergent strategy from siastatin B, a secondary metabolite of Streptomyces. The protonated form of 1-N-iminosugar mimics the charge at the anomeric position in the transition state of enzymatic glycosidic hydrolysis, resulting in a strong and specific inhibition of glycosidases and glycosyltransferases. They have been recently recognized as a new source of therapeutic drug candidates in a wide range of diseases associated with the carbohydrate metabolism of glycoconjugates, such as tumor metastasis, influenza virus infection, lysosomal storage disorder and so forth. The Journal of Antibiotics (2009) 62, 407–423; doi:10.1038/ja.2009.53; published online 3 July 2009 Keywords: glycosidase inhibitor; heparanase inhibitor; influenza virus infection; lysosomal storage disease; 1-N-iminosugar; siastatin B; tumor metastasis INTRODUCTION form of gem-diamine 1-N-iminosugar 6 may mimic the putative Iminosugars, which are carbohydrate analogs that most frequently glycopyranosyl cation 7 that was formed during enzymatic glycosidic carry the nitrogen atom at the position of the endocyclic oxygen, form hydrolysis (Figure 2).
    [Show full text]
  • Heparin - Wikipedia, the Free Encyclopedia
    Heparin - Wikipedia, the free encyclopedia http://en.wikipedia.org/wiki/Heparin From Wikipedia, the free encyclopedia Heparin (from Ancient Greek ηπαρ (hepar), liver), also Heparin known as unfractionated heparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule.[1] It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and renal dialysis machines. Although used principally in medicine for anticoagulation, the true physiological role in the body remains unclear, because blood anti-coagulation is achieved mostly by heparan sulfate proteoglycans derived from endothelial cells.[2] Heparin is usually stored within the secretory granules of mast cells and released only into the vasculature at sites of tissue injury. It has been proposed that, rather than anticoagulation, the main purpose of heparin is defense at such sites against invading bacteria and other foreign materials.[3] In addition, it is conserved across a number of widely different species, including some invertebrates that do not have a similar blood coagulation system. Systematic (IUPAC) name see Heparin structure Clinical data AHFS/Drugs.com monograph 1 Heparin structure Pregnancy cat. C 1.1 Abbreviations Legal status ? 1.2 Three-dimensional structure Routes i.v., s.c. 2 Medical use Pharmacokinetic data 2.1 Mechanism of Action 2.2 Administration Bioavailability nil 2.3 Production Metabolism hepatic 2.4
    [Show full text]
  • Investigating the Antimicrobial Potential of Thalassomonas
    Investigating the antimicrobial potential of Thalassomonas actiniarum By Fazlin Pheiffer A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy (PhD) Department of Biotechnology, University of the Western Cape Supervisor: Prof Marla Trindade Co-supervisor: Dr Leonardo van Zyl 2020 http://etd.uwc.ac.za/ Declaration Declaration I, Fazlin Pheiffer, hereby declare that ‘Investigating the antimicrobial potential of Thalassomonas actiniarum’ is my own work, that it has not been submitted for any degree or examination in any other university, and that all the sources I have used or quoted have been indicated and acknowledged by complete references. Date: 16 March 2021 Signed: i http://etd.uwc.ac.za/ Abstract Abstract The World Health Organisation predicts that by the year 2050, 10 million people could die annually as a result of infections caused by multidrug resistant bacteria. Individuals with compromised immune systems, caused by underlying disease such as HIV, MTB and COVID-19, are at a greater risk. Antibacterial resistance is a global concern that demands the discovery of novel drugs. Natural products, used since ancient times to treat diseases, are the most successful source of new drug candidates with bioactivities including antibiotic, antifungal, anticancer, antiviral, immunosuppressive, anti-inflammatory and biofilm inhibition. Marine bioprospecting has contributed significantly to the discovery of novel bioactive NPs with unique structures and biological activities, superior to that of compounds from terrestrial origin. Marine invertebrate symbionts are particularly promising sources of marine NPs as the competition between microorganisms associated with invertebrates for space and nutrients is the driving force behind the production of antibiotics, which also constitute pharmaceutically relevant natural products.
    [Show full text]
  • Mapping of the Fondaparinux Binding Site of JR-FL Gp120 by High Resolution Hydroxyl Radical Protein Footprinting and Computational Docking Sandeep K
    bioRxiv preprint doi: https://doi.org/10.1101/207910; this version posted October 23, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Mapping of the Fondaparinux Binding Site of JR-FL gp120 by High Resolution Hydroxyl Radical Protein Footprinting and Computational Docking Sandeep K. Misra1, Amika Sood2, Paulo A. Soares3, Vitor H. Pomin3, Robert J. Woods2 and Joshua S. Sharp1* 1Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, University, MS 2Complex Carbohydrate Research Center, University of Georgia, Athens, GA 3Institute of Medical Biochemistry Leopoldo de Meis, University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil *[email protected] bioRxiv preprint doi: https://doi.org/10.1101/207910; this version posted October 23, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract The adhesion of HIV gp120 antigen to human cells is modulated in part by interactions with heparan sulfate. The HXB2 strain of gp120 has been shown to interact with heparin primarily through the V3 loop, although other domains including the C-terminal domain were also implicated. However, the JR-FL strain (representative of CCR5-interacting strains that make up newest infections) was shown to have a drastically lowered affinity to heparin due to the loss of several basic residues in the V3 loop, and deletion of the V3 loop in JR-FL gp120 was shown to abrogate some, but not all, heparin binding.
    [Show full text]
  • Glycosaminoglycan Domain Mapping of Cellular Chondroitin/Dermatan
    www.nature.com/scientificreports OPEN Glycosaminoglycan Domain Mapping of Cellular Chondroitin/ Dermatan Sulfates Andrea Persson1, Egor Vorontsov2, Göran Larson1,3 & Jonas Nilsson1,3* Glycosaminoglycans (GAGs) are polysaccharides produced by most mammalian cells and involved in a variety of biological processes. However, due to the size and complexity of GAGs, detailed knowledge about the structure and expression of GAGs by cells, the glycosaminoglycome, is lacking. Here we report a straightforward and versatile approach for structural domain mapping of complex mixtures of GAGs, GAGDoMa. The approach is based on orthogonal enzymatic depolymerization of the GAGs to generate internal, terminating, and initiating domains, and nanofow reversed-phase ion-pairing chromatography with negative mode higher-energy collision dissociation (HCD) tandem mass spectrometry (MS/MS) for structural characterization of the individual domains. GAGDoMa provides a detailed structural insight into the glycosaminoglycome, and ofers an important tool for deciphering the complexity of GAGs in cellular physiology and pathology. Glycosylation is one of the most prevalent post-translational modifcations of proteins and adds an immense and dynamic diversity to the proteome. Proteoglycans are one type of glycosylated proteins comprising one or more glycosaminoglycans (GAGs), which are extensively sulfated polysaccharides commonly composed of 25–100 repeating disaccharide units. GAGs are essential in cellular physiology and pathology as crucial components in the extracellular
    [Show full text]
  • Biochemical Investigations in the Rare Disease Alkaptonuria: Studies on the Metabolome and the Nature of Ochronotic Pigment
    Biochemical Investigations in the Rare Disease Alkaptonuria: Studies on the Metabolome and the Nature of Ochronotic Pigment Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor of Philosophy by Brendan Paul Norman September 2019 ACKNOWLEDGEMENTS It is hard to describe the journey this PhD has taken me on without reverting to well-worn clichés. There has been plenty of challenges along the way, but ultimately I can look back on the past four years with a great sense of pride, both in the work presented here and the skills I have developed. Equally important though are the relationships I have established. I have lots of people to thank for playing a part in this thesis. First, I would like to thank my supervisors, Jim Gallagher, Lakshminarayan Ranganath and Norman Roberts for giving me this fantastic opportunity. Your dedication to research into alkaptonuria (AKU) is inspiring and our discussions together have always been thoughtful and often offered fresh perspective on my work. It has been a pleasure to work under your supervision and your ongoing support and encouragement continues to drive me on. It has truly been a pleasure to be part of the AKU research group. Andrew Davison deserves a special mention - much of the highs and lows of our PhD projects have been experienced together. Learning LC-QTOF-MS was exciting (and continues to be) but equally daunting at the start of our projects (admittedly more so for me as a Psychology graduate turned mass spectrometrist!). I am very proud of what we have achieved together, largely starting from scratch on the instrument, and we are continuing to learn all the time.
    [Show full text]
  • Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-Ray Analysis
    Article Extended Physicochemical Characterization of the Synthetic Anticoagulant Pentasaccharide Fondaparinux Sodium by Quantitative NMR and Single Crystal X-ray Analysis William de Wildt 1, Huub Kooijman 2, Carel Funke 1, Bülent Üstün 1, Afranina Leika 1, Maarten Lunenburg 1, Frans Kaspersen 1 and Edwin Kellenbach 1,* 1 DTS Aspen Oss B.V., 5223BB Oss, The Netherlands; [email protected] (W.d.W.); [email protected] (C.F.); [email protected] (B.Ü.); [email protected] (A.L.); [email protected] (M.L.); [email protected] (F.K.) 2 Bijvoet Center for Biomolecular Research, Crystal and Structural Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; [email protected] * Correspondence: [email protected]; Tel.: +31-(0)6-2054-9168 Received: 31 May 2017; Accepted: 14 August 2017; Published: 17 August 2017 Abstract: Fondaparinux sodium is a synthetic pentasaccharide representing the high affinity antithrombin III binding site in heparin. It is the active pharmaceutical ingredient of the anticoagulant drug Arixtra®. The single crystal X-ray structure of Fondaparinux sodium is reported, unequivocally confirming both structure and absolute configuration. The iduronic acid adopts a somewhat distorted chair conformation. Due to the presence of many sulfur atoms in the highly sulfated pentasaccharide, anomalous dispersion could be applied to determine the absolute configuration. A comparison with the conformation of Fondaparinux in solution, as well as complexed with proteins is presented. The content of the solution reference standard was determined by quantitative NMR using an internal standard both in 1999 and in 2016. A comparison of the results allows the conclusion that this method shows remarkable precision over time, instrumentation and analysts.
    [Show full text]
  • Silver-Assisted Gold-Catalyzed Formal Synthesis of the Anticoagulant
    ARTICLE https://doi.org/10.1038/s42004-021-00452-y OPEN Silver-assisted gold-catalyzed formal synthesis of the anticoagulant Fondaparinux pentasaccharide ✉ Gulab Walke1, Niteshlal Kasdekar1, Yogesh Sutar1 & Srinivas Hotha 1 Clinically approved anti-coagulant Fondaparinux is safe since it has zero contamination problems often associated with animal based heparins. Fondaparinux is a synthetic penta- saccharide based on the antithrombin-binding domain of Heparin sulfate and contains glu- cosamine, glucuronic acid and iduronic acid in its sequence. Here, we show the formal synthesis of Fondaparinux pentasaccharide by performing all glycosidations in a catalytic fashion for the first time to the best of our knowledge. Designer monosaccharides were 1234567890():,; synthesized avoiding harsh reaction conditions or reagents. Further, those were subjected to reciprocal donor-acceptor selectivity studies to guide [Au]/[Ag]-catalytic glycosidations for assembling the pentasaccharide in a highly convergent [3 + 2] or [3 + 1 + 1] manner. Cat- alytic and mild activation during glycosidations that produce desired glycosides exclusively, scalable route to the synthesis of unnatural and expensive iduronic acid, minimal number of steps and facile purifications, shared use of functionalized building blocks and excellent process efficiency are the salient features. 1 Department of Chemistry, Indian Institute of Science Education and Research (IISER), Pune, MH, India. ✉email: [email protected] COMMUNICATIONS CHEMISTRY | (2021) 4:15 | https://doi.org/10.1038/s42004-021-00452-y
    [Show full text]
  • Introduction (Pdf)
    Dictionary of Natural Products on CD-ROM This introduction screen gives access to (a) a general introduction to the scope and content of DNP on CD-ROM, followed by (b) an extensive review of the different types of natural product and the way in which they are organised and categorised in DNP. You may access the section of your choice by clicking on the appropriate line below, or you may scroll through the text forwards or backwards from any point. Introduction to the DNP database page 3 Data presentation and organisation 3 Derivatives and variants 3 Chemical names and synonyms 4 CAS Registry Numbers 6 Diagrams 7 Stereochemical conventions 7 Molecular formula and molecular weight 8 Source 9 Importance/use 9 Type of Compound 9 Physical Data 9 Hazard and toxicity information 10 Bibliographic References 11 Journal abbreviations 12 Entry under review 12 Description of Natural Product Structures 13 Aliphatic natural products 15 Semiochemicals 15 Lipids 22 Polyketides 29 Carbohydrates 35 Oxygen heterocycles 44 Simple aromatic natural products 45 Benzofuranoids 48 Benzopyranoids 49 1 Flavonoids page 51 Tannins 60 Lignans 64 Polycyclic aromatic natural products 68 Terpenoids 72 Monoterpenoids 73 Sesquiterpenoids 77 Diterpenoids 101 Sesterterpenoids 118 Triterpenoids 121 Tetraterpenoids 131 Miscellaneous terpenoids 133 Meroterpenoids 133 Steroids 135 The sterols 140 Aminoacids and peptides 148 Aminoacids 148 Peptides 150 β-Lactams 151 Glycopeptides 153 Alkaloids 154 Alkaloids derived from ornithine 154 Alkaloids derived from lysine 156 Alkaloids
    [Show full text]
  • Protein–Glycosaminoglycan Interaction Networks: Focus
    +Model PISC-387; No. of Pages 8 ARTICLE IN PRESS Perspectives in Science (2016) xxx, xxx—xxx View metadata, citation and similar papers at core.ac.uk brought to you by CORE Available online at www.sciencedirect.com provided by Elsevier - Publisher Connector ScienceDirect journal homepage: www.elsevier.com/pisc Protein—glycosaminoglycan interaction networks: Focus on heparan sulfateଝ Sylvie Ricard-Blum Institute for Molecular and Supramolecular Chemistry and Biochemistry, UMR 5246 CNRS, University Lyon 1-INSA Lyon, CPE, Raulin Building, University Lyon 1, 43 Boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex, France Received 4 January 2016; accepted 19 February 2016 KEYWORDS Summary Sulfated glycosaminoglycans (GAGs) are complex polysaccharides, which are cova- Extracellular matrix; lently bound to protein cores to form proteoglycans. They are mostly located at the cell surface Heparan sulfate; and in the extracellular matrix (ECM) where they regulate numerous biological processes. The Interaction networks; aim of our work is (i) to identify and characterize protein—GAG interactions occurring at the cell Interaction surface and in the ECM, (ii) to study the assembly of multimolecular complexes formed at the databases; cell surface via protein—heparan sulfate interactions, (iii) to determine the roles of these com- Surface plasmon plexes in the ECM maturation and assembly, which are initiated in the pericellular matrix, and resonance in pathological situations such as angiogenesis and host—pathogen interactions, (iv) to build, contextualize and analyze the corresponding protein—heparan sulfate interaction networks to identify molecular connections between the physio-pathological processes mentioned above and to select protein—GAG complexes specifically formed in a pathological situation and which might be therapeutic targets.
    [Show full text]
  • BMB 170 Lecture 19 (LAST LECTURE!) Carbohydrates, Nov. 30, 2017
    BMB 170 Lecture 19 (LAST LECTURE!) Carbohydrates, Nov. 30, 2017 • Carbohydrates • Glycosyltransferases and glycosidases • Protein glycosyla5on • Glycobiology of bacteria • Glycan binding and the role of glycans • Glycobiomics Third Edition of Essentials of Glycobiology—Appendix 1B: Symbol Nomenclature for Glycans (SNFG) History and Citation: Symbol Nomenclature for Graphical Representation of Glycans, Glycobiology 25: 1323-1324, 2015. Citation link (PMID 26543186). Table 1. Monosaccharide symbol nomenclature June 5, 2017 SHAPE White Blue Green Yellow Orange Pink Purple Light Blue Brown Red (Generic) Hexose Glc Man Gal Gul Alt All Tal Ido Filled Circle Filled HexNAc GlcNAc ManNAc GalNAc GulNAc AltNAc AllNAc TalNAc IdoNAc Square Crossed Hexosamine GlcN ManN GalN GulN AltN AllN TalN IdoN Square Divided Hexuronate GlcA ManA GalA GulA AltA AllA TalA IdoA Diamond Filled Deoxyhexose Qui Rha 6dGul 6dAlt 6dTal Fuc Triangle Divided DeoxyhexNAc QuiNAc RhaNAc 6dAltNAc 6dTalNAc FucNAc Triangle Flat Di-deoxyhexose Oli Tyv Abe Par Dig Col Rectangle Pentose Ara Lyx Xyl Rib Filled Star Filled Deoxynonulosonate Kdn Neu5Ac Neu5Gc Neu Sia Diamond Di- Pse Leg Aci 4eLeg Flat deoxynonulosonate Diamond Flat Unknown Bac LDmanHep Kdo Dha DDmanHep MurNAc MurNGc Mur Hexagon Assigned Api Fru Tag Sor Psi Pentagon When viewed in presentation/slide-show mode, clicking individual monosaccharide names or symbols will lead to corresponding PubChem page. Right/Control click to copy a symbol, along with the embedded PubChem URL, which will also remain when pasting into some
    [Show full text]
  • Photochemical Depolymerisation of Dermatan Sulfate and Analysis of the Generated Oligosaccharides
    Edinburgh Research Explorer Photochemical depolymerisation of dermatan sulfate and analysis of the generated oligosaccharides Citation for published version: Panagos, CG, August, DP, Jesson, C & Uhrin, D 2016, 'Photochemical depolymerisation of dermatan sulfate and analysis of the generated oligosaccharides', Carbohydrate polymers, vol. 140, pp. 13-19. https://doi.org/10.1016/j.carbpol.2015.11.078 Digital Object Identifier (DOI): 10.1016/j.carbpol.2015.11.078 Link: Link to publication record in Edinburgh Research Explorer Document Version: Peer reviewed version Published In: Carbohydrate polymers General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 25. Sep. 2021 1 1 Photochemical depolymerisation of dermatan sulfate and analysis of the generated 2 oligosaccharides. 3 Charalampos G. Panagos, a,b David P. August,a Christine Jesson,b Dušan Uhrín a,* a 4 EastChem School of Chemistry, The University of Edinburgh, King´s Buildings, David Brewster Road , 5 Edinburgh EH9 3FJ, United Kingdom. 6 b GlycoMar Ltd, European Centre for Marine Biotechnology, Oban, Scotland, PA37 1QA, United Kingdom. 7 8 *To whom correspondence should be addressed: EaStCHEM School of Chemistry, Joseph Black Bldg., 9 The King’s Buildings, University of Edinburgh, Edinburgh, EH9 3FJ, United Kingdom.
    [Show full text]