4 research outputs found
Preparation of <i>N</i>āLinked-Type GlcNAc Monomers for Glycopolymers and Binding Specificity for Lectin
Glycomonomers having N-glycosidic linkages
were
prepared from a known glycosyl amine, N-acetyl-d-glucosamine (GlcNAc). Radical polymerization of the glycomonomers
gave a series of glycopolymers displaying various sugar densities,
which were models of the core structure of Asn-linked-type glycoproteins.
In addition, fluorometric analyses of wheat germ agglutinin (WGA)
against the glycopolymers were carried out, and the results showed
unique binding specificities on the basis of flexibility of sugar
moieties
Preparation of a Water-Soluble Glycopolymer Bearing Porphyrin Skeletons and Its Biological Properties
A known tetraphenyl porphyrin (TPP) having an amino functional
group [5-(4-aminophenyl)-10,15,20-(triphenyl)porphyrin] was converted
into the corresponding monomer by means of condensation with acryloyl
chloride. Simple radical polymerization of the porphyrin monomer and
a glycosyl monomer in the presence of acrylamide as a regulator monomer
in order to avoid steric interference gave a water-soluble glycopolymer
bearing porphyrin moieties. Spectroscopic analyses suggested incorporation
of porphyrin moieties in the glycopolymer. The physical properties
of the water-soluble glycopolymer bearing porphyrin moieties were
examined in aqueous media, and the results also indicated the incorporation
of TPP moieties in the polymer. Uptake of the polymer into HeLa cells
was observed, and the cytotoxicity of the polymer was confirmed by
microscopic analyses. The glycopolymer bearing porphyrin moieties
is promising not only for photodynamic therapy but also as an anti-cancer
reagent
Influence of 4ā²ā<i>O</i>āGlycoside Constitution and Configuration on Ribosomal Selectivity of Paromomycin
A series of 20 4ā²-<i>O</i>-glycosides of the aminoglycoside
antibiotic paromomycin were synthesized and evaluated for their ability
to inhibit protein synthesis by bacterial, mitochondrial and cytosolic
ribosomes. Target selectivity, i.e., inhibition of the bacterial ribosome
over eukaryotic mitochondrial and cytosolic ribosomes, which is predictive
of antibacterial activity with reduced ototoxicity and systemic toxicity,
was greater for the equatorial than for the axial pyranosides, and
greater for the d-pentopyranosides than for the l-pentopyranosides and d-hexopyranosides. In particular,
4ā²-<i>O</i>-Ī²-d-xylopyranosyl paromomycin
shows antibacterioribosomal activity comparable to that of paromomycin,
but is significantly more selective showing considerably reduced affinity
for the cytosolic ribosome and for the A1555G mutant mitochondrial
ribosome associated with hypersusceptibility to drug-induced ototoxicity.
Compound antibacterioribosomal activity correlates with antibacterial
activity, and the ribosomally more active compounds show activity
against <i>Escherichia coli</i>, <i>Klebsiella pneumonia</i>, <i>Enterobacter cloacae</i>, <i>Acinetobacter baumannii</i>, and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). The paromomycin glycosides retain activity against clinical
strains of MRSA that are resistant to paromomycin, which is demonstrated
to be a consequence of 4ā²-<i>O</i>-glycosylation
blocking the action of 4ā²-aminoglycoside nucleotidyl transferases
by the use of recombinant <i>E. coli</i> carrying the specific
resistance determinant
The Quest for Anticancer Vaccines: Deciphering the Fine-Epitope Specificity of Cancer-Related Monoclonal Antibodies by Combining Microarray Screening and Saturation Transfer Difference NMR
The identification of MUC1 tumor-associated
Tn antigen (Ī±GalpNAc1-<i>O</i>-Ser/Thr) has boosted
the development of anticancer vaccines.
Combining microarrays and saturation transfer difference NMR, we have
characterized the fine-epitope mapping of a MUC1 chemical library
(naked and Tn-glycosylated) toward two families of cancer-related
monoclonal antibodies (anti-MUC1 and anti-Tn mAbs). Anti-MUC1 mAbs
clone VU-3C6 and VU-11E2 recognize naked MUC1-derived peptides and
bind GalNAc in a peptide-sequence-dependent manner. In contrast, anti-Tn
mAbs clone 8D4 and 14D6 mostly recognize the GalNAc and do not bind
naked MUC1-derived peptides. These anti-Tn mAbs show a clear preference
for glycopeptides containing the Tn-Ser antigen rather than the Tn-Thr
analogue, stressing the role of the underlying amino acid (serine
or threonine) in the binding process. The reported strategy can be
employed, in general, to unveil the key minimal structural features
that modulate antigenāantibody recognition, with particular
relevance for the development of Tn-MUC1-based anticancer vaccines