Synthetische Antitumor-Vakzine aus MUC1-Glycopeptiden mit zwei immundominanten Domänen - Induktion einer starken Immunreaktion gegen Brusttumorgewebe

Synthetic Antitumor Vaccines from Tetanus Toxoid Conjugates of MUC1 Glycopeptides with the Thomsen-Friedenreich Antigen and a Fluorine-Substituted Analogue

Vom E-Selektin-Liganden 1 abgeleitete Glycopeptide mit variierter Sialyl-Lewisx-Struktur als Zelladhäsionsinhibitoren für E-Selektin

Total Synthesis of the Glycopeptide Recognition Domain of the P-Selectin Glycoprotein Ligand 1

A Synthetic Vaccine Consisting of a Tumor-Associated Sialyl-TN-MUC1 Tandem-Repeat Glycopeptide and Tetanus Toxoid: Induction of a Strong and Highly Selective Immune Response

Ein synthetischer Impfstoff aus einem tumorassoziierten Sialyl-TN-MUC1-Tandem-Repeat-Glycopeptid und Tetanustoxoid zur Induktion einer starken, hochselektiven Immunantwort

Synthetic Glycopeptides from the E-Selectin Ligand 1 with Varied Sialyl Lewisx Structure as Cell-Adhesion Inhibitors of E-Selectin.

Chemoselective Removal of Protecting Groups from O-Glycosyl Amino Acid and Peptide (Methoxyethoxy)ethyl Esters Using Lipases and Papain

The selective C-terminal deprotection of O-glycopeptide (methoxyethoxy)ethyl esters is achieved under mild conditions (pH 6.6, 37 degrees C) by enzymatic hydrolysis using papain or lipase M from Mucor javanicus to give building blocks useful for chain-extending glycopeptide synthesis. On the other hand, the selective removal of acetyl protecting groups from the saccharide portion of glycopeptides is accomplished by alternative enzymatic hydrolysis with lipase WG from wheat germ to furnish model substrates for enzymatic glycosyl transfer reactions in order to extend the carbohydrate side chain of these conjugates.

Sulfated and Non-Sulfated Glycopeptide Recognition Domains of P-Selectin Glycoprotein Ligand 1 and their Binding to P- and E-Selectin

Total synthesis through block glycosylation and selective chemical O-sulfation of tyrosine residues yielded the glycopeptide recognition domain A (X=SO(3) (-)) of the P-selectin glycoprotein ligand 1, in which the terminal sialic acid of the complex hexasaccharide side chain was replaced by (S)-cyclohexyl lactic acid. In binding assays the O-sulfated structure A showed high affinity towards P-selectin, the non-sulfated towards E-selectin.

Synthetische Vakzine aus tumorassoziierten MUC1-Glycopeptid-Antigenen und Rinderserumalbumin

Sulfatierte und nicht sulfatierte Glycopeptid-Erkennungsdomänen des P-Selektin-Glycoprotein-Liganden 1 und ihre Bindung an P- und E-Selektin

Totalsynthese via Blockglycosylierung und selektive chemische O-Sulfatierung von Tyrosinresten ergaben die Glycopeptid-Erkennungsregion A (X=SO3−) des P-Selektin-Glycoprotein-Liganden 1, in dem die terminale Sialinsaure der komplexen Hexasaccharid-Seitenkette durch (S)-Cyclohexylmilchsaure als Mimetikum ersetzt ist. In Bindungsassays zeigt die O-sulfatierte Form A hohe Affinitat zu P-Selektin, die nicht sulfatierte Form zu E-Selektin.

Chemoenzymatic Synthesis of Functional Sialyl LewisX Mimetics with a Heteroaromatic Core

Functional mimetics of the sialyl Lewis(X) tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-Lewis(X) -containing neighboring sulfated tyrosine residues (sTyr/sLe(X) -PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide.

Totalsynthese der Glycopeptid-Erkennungsregion des P-Selektin- Glycoprotein-Liganden 1

A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles through in Situ-Generated Acylazirines

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced in situ formation of acylazirines combined with a subsequent cobalt(II)-catalyzed ring expansion with 1,3-diketones.

Synthetische Antitumorvakzine aus Tetanus-Toxoid-Konjugaten von MUC1-Glycopeptiden mit Thomsen-Friedenreich-Antigen und dessen fluorsubstituiertem Analogon

Enzymatische hydrolyse hydrophiler ester durch lipasen - eine milde carboxydeblockierung von peptiden und glycopeptiden

Abstract The markedly hydrophilic 2-(N-morpholino)ethyl (MoEt) esters of protected peptides and glycopeptides are selectively and efficiently cleaved by lipases in water/acetone (10:1) at pH 7.

Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention

Abstract Arabinogalactan, a microheterogeneous polysaccharide occurring in plants, is known for its allergy‐protective activity, which could potentially be used for preventive allergy treatment. New treatment options are highly desirable, especially in a preventive manner, due to the constant rise of atopic diseases worldwide. The structural origin of the allergy‐protective activity of arabinogalactan is, however, still unclear and isolation of the polysaccharide is not feasible for pharmaceutical applications due to a variation of the activity of the natural product and contaminations with endotoxins. Therefore, a pentasaccharide partial structure was selected for total synthesis and subse…

ChemInform Abstract: A Photoinduced Cobalt-Catalyzed Synthesis of Pyrroles Through in situ-Generated Acylazirines.

Tetrasubstituted pyrroles can be synthesized in a one-pot procedure from isoxazoles. The process includes the photoinduced in situ formation of acylazirines combined with a subsequent cobalt(II)-catalyzed ring expansion with 1,3-diketones.

Multivalency Beats Complexity: A Study on the Cell Uptake of Carbohydrate Functionalized Nanocarriers to Dendritic Cells.

Herein, we report the synthesis of carbohydrate and glycodendron structures for dendritic cell targeting, which were subsequently bound to hydroxyethyl starch (HES) nanocapsules prepared by the inverse miniemulsion technique. The uptake of the carbohydrate-functionalized HES nanocapsules into immature human dendritic cells (hDCs) revealed a strong dependence on the used carbohydrate. A multivalent mannose-terminated dendron was found to be far superior in uptake compared to the structurally more complex oligosaccharides used.

Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and bovine serum albumin.

Total Synthesis of (+)-Phenguignardic Acid, a Phytotoxic Metabolite ofGuignardia bidwellii

(+)-Phenguignardic acid, a phytotoxic metabolite of the grape black rot fungus Guignardia bidwellii was synthesized, as well as its enantiomer, in eight steps from (R)-phenyllactic acid and 3-phenylprop-2-yn-1-ol. The formation of the carboxylate at a late stage, to avoid enolization of the precursor used in the central acetalization step, proved to be crucial. The synthesis of the natural product allowed the unabiguous assignment of its hitherto unknown absolute configuration.

Synthetic antitumor vaccines containing MUC1 glycopeptides with two immunodominant domains-induction of a strong immune response against breast tumor tissues.

A shot in the arm for cancer treatment: two MUC1 tetanus toxoid vaccines were synthesized and induced a strong immune response in mice. The antibodies elicited by the vaccines show a high selectivity for the tumor cells in mammary carcinoma tissues and also distinguish between tumor tissues at different stages.

ChemInform Abstract: Total Synthesis of (+)-Phenguignardic Acid, a Phytotoxic Metabolite of Guignardia bidwellii

(+)-Phenguignardic acid, a phytotoxic metabolite of the grape black rot fungus Guignardia bidwellii was synthesized, as well as its enantiomer, in eight steps from (R)-phenyllactic acid and 3-phenylprop-2-yn-1-ol. The formation of the carboxylate at a late stage, to avoid enolization of the precursor used in the central acetalization step, proved to be crucial. The synthesis of the natural product allowed the unabiguous assignment of its hitherto unknown absolute configuration.

Cover Feature: Total Synthesis of a Partial Structure from Arabinogalactan and Its Application for Allergy Prevention (Chem. Eur. J. 3/2021)

ChemInform Abstract: Chemoselective Removal of Protecting Groups from O-Glycosyl Amino Acid and Peptide (Methoxyethoxy)ethyl Esters Using Lipases and Papain.

The selective C-terminal deprotection of O-glycopeptide (methoxyethoxy)ethyl esters is achieved under mild conditions (pH 6.6, 37 degrees C) by enzymatic hydrolysis using papain or lipase M from Mucor javanicus to give building blocks useful for chain-extending glycopeptide synthesis. On the other hand, the selective removal of acetyl protecting groups from the saccharide portion of glycopeptides is accomplished by alternative enzymatic hydrolysis with lipase WG from wheat germ to furnish model substrates for enzymatic glycosyl transfer reactions in order to extend the carbohydrate side chain of these conjugates.

CCDC 1483914: Experimental Crystal Structure Determination

Related Article: Stefan Pusch, Danuta Kowalczyk, and Till Opatz|2016|J.Org.Chem.|81|4170|doi:10.1021/acs.joc.6b00511

CCDC 1483913: Experimental Crystal Structure Determination

Related Article: Stefan Pusch, Danuta Kowalczyk, and Till Opatz|2016|J.Org.Chem.|81|4170|doi:10.1021/acs.joc.6b00511