A5051355622- Angiogenesis and VEGF in Cancer
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Medicinal Plant Pharmacodynamics Research
- Cell Adhesion Molecules Research
- Flavonoids in Medical Research
- Galectins and Cancer Biology
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Cancer therapeutics and mechanisms
- Proteoglycans and glycosaminoglycans research
- Multiple Myeloma Research and Treatments
- Immune Response and Inflammation
- Estrogen and related hormone effects
- Retinoids in leukemia and cellular processes
- Infant Nutrition and Health
- Enzyme Production and Characterization
- Legume Nitrogen Fixing Symbiosis
- Reproductive biology and impacts on aquatic species
- Korean Urban and Social Studies
- Probiotics and Fermented Foods
- Gut microbiota and health
- Enzyme Structure and Function
Glykos (Finland)
2007-2024
University of Helsinki
1991-2002
Helsinki Institute of Physics
2001
Biocenter Finland
1997
Czech Academy of Sciences, Institute of Biotechnology
1994
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOligosaccharide Constructs with Defined Structures That Inhibit Binding of Mouse Sperm to Unfertilized Eggs in VitroEveline S. Litscher, Kari Juntunen, Antti Seppo, Leena Penttila, Ritva Niemela, Ossi Renkonen, and Paul M. WassarmanCite this: Biochemistry 1995, 34, 14, 4662–4669Publication Date (Print):April 11, 1995Publication History Published online1 May 2002Published inissue 11 April...
The P-selectin counterreceptor PSGL-1 is covalently modified by mono alpha2,3-sialylated, multiply alpha1,3-fucosylated polylactosamines. These glycans are required for the adhesive interactions that allow this adhesion receptor-counterreceptor pair to facilitate leukocyte extravasation. To begin understand biosynthesis of these glycans, we have characterized acceptor and site specificities two granulocyte alpha1,3-fucosyltransferases, Fuc-TIV Fuc-TVII, using recombinant forms enzymes a...
Abstract We show here that colon‐carcinoma cell lines adhere to E‐selectin via sialyl Lewis x and a (sLex sLea) oligosaccharides this adhesion can be enhanced by TNF stimulation. To study in greater detail endothelial binding, we analysed the mRNA expression function of enzymes participating generation sLex sLea on cancer cells. These are synthesized sequential action α2,3 (α2,3‐ST) α1,3/1,4 fucosyltransferases (α1,3/1,4‐FT) existing (poly)N‐acetyllactosamine chains. report mRNAs 2 recently...
Abstract Sialyl Lewis x (sLex) oligosaccharides have been shown to be present in counterreceptors for L‐selectin. We and others previously that high endothelial cells lymph nodes at sites of inflammation express sLex. Here we show also cultured human umbilical vein (HUVEC) sLex on their cell surface. This oligosaccharide is formed by sequential action α2,3‐sialyl‐ (α2,3‐ST) α1,3‐fucosyltransferases (α1,3‐FT) N‐acetyllactosamine. At least two the several α2,3‐ST four α1,3‐FT are HUVEC. In...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHuman serum contains a novel .beta.1,6-N-acetylglucosaminyltransferase activity that is involved in midchain branching of oligo(N-acetyllactosaminoglycans)Anne Leppanen, Leena Penttila, Ritva Niemela, Jari Helin, Antti Seppo, Sari Lusa, and Ossi RenkonenCite this: Biochemistry 1991, 30, 38, 9287–9296Publication Date (Print):September 1, 1991Publication History Published online1 May 2002Published inissue 1 September...
GlcNAcβ1-3(GlcNAcβ1-6)[ 14 C(U)]Gal and C(U)]Galβ1-4GlcNAc were prepared by in vitro synthesis. They characterized enzymatic sequencing, partial acid hydrolysis, periodate oxidation experiments. The two saccharides isolated also from hydrolysates of metabolically labeled poly-N- acetyllactosaminoglycans murine embryonal carcinoma cells (line PC 13). tetrasaccharide was retarded a column agarose-linked wheat germ agglutinin; the trisaccharide strongly bound. Chromatography this separated into...
Antibody-drug conjugates (ADC) have shown impressive clinical activity with approval of many agents in hematologic and solid tumors. However, challenges remain both efficacy safety ADCs. This study describes novel trastuzumab-auristatin the hydrophilic monomethylauristatin E (MMAE) prodrug MMAU, optimization a glycopeptide linker leading to wider therapeutic window. Trastuzumab was conjugated auristatin payloads via series linkers using stabilized maleimide handle. The ADCs were...
CD33 (Siglec-3) is a cell surface receptor expressed in approximately 90% of acute myeloid leukemia (AML) blasts, making it an attractive target for therapy AML. Although previous CD33-targeting antibody-drug conjugates (ADC) like gemtuzumab ozogamicin (GO, Mylotarg) have shown efficacy AML treatment, they suffered from toxicity and narrow therapeutic window. This study aimed to develop novelADCwith improved tolerability wider GLK-33 consists the anti-CD33 antibody lintuzumab eight mavg-MMAU...
In the present experiments cDNA coding for a truncated form of β1,6N-acetylglucosaminyltransferase responsible conversion linear to branched polylactosamines in human PA1 cells was expressed Sf9 insect cells. The catalytic ectodomain enzyme fused glutathione S-transferase, allowing effective one-step purification glycosylated 67–74-kDa fusion protein. Typically yield 750 μg purified protein/liter suspension culture obtained. recombinant protein catalyzed transfer GlcNAc from UDP-GlcNAc...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEnzymic Synthesis of Octadecameric Saccharides Multiply Branched Blood Group I-Type, Carrying Four Distal .alpha.1,3-Galactose or .beta.1,3-GlcNAc ResiduesAntti Seppo, Leena Penttila, Ritva Niemela, Hannu Maaheimo, Ossi Renkonen, and Anita KeaneCite this: Biochemistry 1995, 34, 14, 4655–4661Publication Date (Print):April 11, 1995Publication History Published online1 May 2002Published inissue 11 April...
Commensal gut microbiota and probiotics have numerous effects on the host’s metabolic protective systems, which occur primarily through intestinal epithelial cell interface. Prebiotics, like galacto-oligosaccharides (GOS) are widely used to modulate their function abundance. However, important structure–function relations may exist, requiring a detailed structural characterization. Here, we characterization of bovine whey derived oligosaccharide preparations enriched with GOS or not, dubbed...
The polylactosamine sLexβ1–3′(sLexβ1–6′)LacNAcβ1–3′(sLexβ1–6′)LacNAcβ1–3′(sLexβ1–6′)LacNAc (7) (where sLex is Neu5Acα2–3Galβ1–4(Fucα1–3)GlcNAc and LacNAc Galβ1–4GlcNAc) a nanomolar L‐selectin antagonist therefore potential anti‐inflammatory agent (Renkonen et al. (1997) Glycobiology, 7, 453). Here we describe an improved synthesis of 7. octasaccharide LacNAcβ1–3′LacNAcβ1–3′LacNAcβ1–3′LacNAc (4) was converted into the triply branched undecasaccharide...
We report here on in vitro acceptor and site specificity of recombinant alpha3-fucosyltransferase V (Fuc-TV) with 40 oligosaccharide acceptors. Galbeta1-4GlcNAc (LN) GalNAcbeta1-4GlcNAc (LDN) reacted rapidly; Galbeta1-3GlcNAc (LNB) moderately, GlcNAcbeta1-4GlcNAc (N, N'-diacetyl-chitobiose) slowly yet distinctly. In neutral terminally alpha3-sialylated polylactosamines i-type, the reducing end LN unit rapidly distal (sialyl)LN group very slowly; midchain LNs revealed intermediate...
Branched polylactosamines on animal cell surfaces are believed to contribute multivalent interactions in adhesion and signalling. Their biosynthesis proceeds via linear precursors that become branched by β1,6-GlcNAc transferases (IGnT6, GlcNAc Gal). Previous work has identified the tetrasaccharide Galβ1−4GlcNAcβ1−3Galβ1−4GlcNAc (1) hexasaccharide Galβ1−4GlcNAcβ1−3Galβ1−4GlcNAcβ1−3Galβ1−4GlcNAc (4) as acceptors for a rat serum enzyme activity (cIGnT6), which transfers GlcNAcβ1−6 units...
We report that isomeric monofucosylhexasaccharides, Galβ1–4GlcNAcβ1–3Galβ1–4GlcNAcβ1–3Galβ1–4(Fucα1–3)GlcNAc, Galβ1–4GlcNAcβ1–3Galβ1–4(Fucα1–3)GlcNAcβ1–3Galβ1–4GlcNAc and Galβ1–4(Fucα1–3)GlcNAcβ1–3Galβ1–4GlcNAcβ1–3Galβ1–4GlcNAc, bifucosylhexasaccharides Galβ1–4GlcNAcβ1–3Galβ1–4(Fucα1–3)GlcNAcβ1–3Galβ1–4(Fucα1–3)GlcNAc, Galβ1–4(Fucα1–3)GlcNAcβ1–3Galβ1–4GlcNAcβ1–3Galβ1–4(Fucα1–3)GlcNAc Galβ1–4(Fucα1–3)GlcNAcβ1–3Galβ1–4(Fucα1–3)GlcNAcβ1–3Galβ1–4GlcNAc can be isolated in pure form from reaction...
Proposing to study the molecular mechanisms of mouse gamete adhesion with aid high affinity inhibitors saccharide nature, we report here enzymatic synthesis a bivalent oligosaccharide Gal alpha 1-3Gal beta 1-4GlcNAc 1-3(Gal 1-6)Gal (4), consisting two long arms that link together distal 1,3-galactose residues. Binding data reported elsewhere (E. Litscher et al., Biochemistry, 1995, 34, 4662-4669) show 4 is inhibitor in vitro (IC50 = 9 microM), while related octasaccharide 1-4GlcNAc, short...
Radiolabelled lacto-N-neohexaosc was fucosylated with partially purified α(l,3)fucosyltransferase{s) from human milk. Structural analysis of the monofucosylated products obtained at an early stage reaction revealed that both distal branches acceptor had reacted equally well, generating Lewis x determinants, while reducing end glucose not reacted. The two isomeric glycans were readily separated each other by chromatography on immobilized wheat germ agglutinin (WGA), because α(l,3)fucosylation...
Human α3-fucosyltransferases (Fuc-Ts) are known to convert N-acetyllactosamine Galβ1-4(Fucα1-3)GlcNAc (Lewis x antigen); some of them transfer fucose also GalNAcβ1-4GlcNAc, generating GalNAcβ1-4(Fucα1-3)GlcNAc determinants. Here, we report that recombinant forms Fuc-TV and Fuc-TVI as well Fuc-Ts human milk converted chitin oligosaccharides 2–4 GlcNAc units efficiently products containing a GlcNAcβ1-4(Fucα1-3)GlcNAcβ1-4R determinant at the nonreducing terminus. The product structures were...
The GalNAcβ1-4GlcNAc determinant (LdN) occurs in some human and bovine glycoconjugates also lower vertebrates invertebrates. It has been found unsubstituted as well terminally substituted forms at the distal end of conjugated glycans, but it not reported previously truly internal positions polylactosamine chains. Here, we describe enzyme-assisted conversion LdNβ1-OR oligosaccharides into GlcNAcβ1-3GalNAcβ1-4GlcNAcβ1-OR. extension reactions, catalyzed by serum, were modeled after analogous...
Four radiolabeled pentasaccharides, GlcNAcβ1-3(Galβ1-4GlcNAcβ1-6)Galβ1-4GlcNAc, Galβ1-4GlcNAcβ1-3-(GlcNAcβ1-6)Galβ1-4GlcNAc, GlcNAcβ1-3(Galβ1-4GlcNAcβ1-6)Galβ1-4Glc, and Galβ1-4GlcNAcβ1-3(GlcNAcβ1-6)-Galβ1-4Glc, were prepared in virtually pure form. They obtained by partial enzymic β1,4-galactosylations of the appropriate tetrasaccharide acceptors or degalactosylations hexasaccharides, followed paper chromatographic separations. All four pentasaccharides contain two nonidentical distal...
<p>Ex vivo cytotoxicity assays with leukemia blast samples.</p>