13 research outputs found
Elucidating the role of N-acetylglucosamine in Group A Carbohydrate for the development of an effective glycoconjugate vaccine against Group A Streptococcus
No full textGroup A Carbohydrate (GAC), conjugated to an appropriate carrier protein, has been proposed as an attractive
vaccine candidate against Group A Streptococcus infections. Native GAC consists of a polyrhamnose (polyRha)
backbone with N-acetylglucosamine (GlcNAc) at every second rhamnose residue. Both native GAC and the
polyRha backbone have been proposed as vaccine components. Here, chemical synthesis and glycoengineering
were used to generate a panel of different length GAC and polyrhamnose fragments. Biochemical analyses were
performed confirming that the epitope motif of GAC is composed of GlcNAc in the context of the polyrhamnose
backbone. Conjugates from GAC isolated and purified from a bacterial strain and polyRha genetically expressed
in E. coli and with similar molecular size to GAC were compared in different animal models. The GAC conjugate
elicited higher anti-GAC IgG levels with stronger binding capacity to Group A Streptococcus strains than the
polyRha one, both in mice and in rabbits.
This work contributes to the development of a vaccine against Group A Streptococcus suggesting GAC as
preferable saccharide antigen to include in the vaccine
Controlling Multivalent Binding through Surface Chemistry: Model Study on Streptavidin.
No full textAlthough multivalent binding to surfaces is an important tool in nanotechnology, quantitative information about the residual valency and orientation of surface-bound molecules is missing. To address these questions, we study streptavidin (SAv) binding to commonly used biotinylated surfaces such as supported lipid bilayers (SLBs) and self-assembled monolayers (SAMs). Stability and kinetics of SAv binding are characterized by quartz crystal microbalance with dissipation monitoring, while the residual valency of immobilized SAv is quantified using spectroscopic ellipsometry by monitoring binding of biotinylated probes. Purpose-designed SAv constructs having controlled valencies (mono-, di-, trivalent in terms of biotin-binding sites) are studied to rationalize the results obtained on regular (tetravalent) SAv. We find that divalent interaction of SAv with biotinylated surfaces is a strict requirement for stable immobilization, while monovalent attachment is reversible and, in the case of SLBs, leads to the extraction of biotinylated lipids from the bilayer. The surface density and lateral mobility of biotin, and the SAv surface coverage are all found to influence the average orientation and residual valency of SAv on a biotinylated surface. We demonstrate how the residual valency can be adjusted to one or two biotin binding sites per immobilized SAv by choosing appropriate surface chemistry. The obtained results provide means for the rational design of surface-confined supramolecular architectures involving specific biointeractions at tunable valency. This knowledge can be used for the development of well-defined bioactive coatings, biosensors and biomimetic model systems
Chemoselective Cleavage of <i>p</i>‑Methoxybenzyl and 2‑Naphthylmethyl Ethers Using a Catalytic Amount of HCl in Hexafluoro-2-propanol
No full textA new, fast, mild and chemoselective
deprotection method to cleave <i>p</i>-methoxybenzyl and
2-naphthylmethyl ethers using catalytic
amounts of hydrochloric acid in a 1:1 mixture of hexafluoro-2-propanol
(HFIP) and methylene chloride (DCM) is described. The scope of the
methodology becomes apparent from 14 examples of orthogonally protected
monosaccharides that are subjected to HCl/HFIP treatment. The applicability
of the HCl/HFIP method is illustrated by the synthesis of a sulfated
β-mannuronic acid disaccharide
The Cyanopivaloyl Ester: A Protecting Group in the Assembly of Oligorhamnans
No full textBio-organic Synthesi
ChemInform Abstract: Chemoselective Cleavage of P‐Methoxybenzyl and 2‐Naphthylmethyl Ethers Using a Catalytic Amount of HCl in Hexafluoro‐2‐propanol.
No full textPhotochemical Resolution of a Thermally Inert Cyclometalated Ru(phbpy)(N–N)(Sulfoxide)<sup>+</sup> Complex
No full textIn
this work a photosubstitution strategy is presented that can
be used for the isolation of chiral organometallic complexes. A series
of five cyclometalated complexes Ru(phbpy)(N−N)(DMSO-κS)](PF6) ([1]PF6-[5]PF6) were synthesized and characterized, where Hphbpy = 6′-phenyl-2,2′-bipyridyl,
and N–N = bpy (2,2′-bipyridine), phen (1,10-phenanthroline),
dpq (pyrazino[2,3-f][1,10]phenanthroline), dppz (dipyrido[3,2-a:2′,3′-c]phenazine, or dppn
(benzo[i]dipyrido[3,2-a,2′,3′-c]phenazine), respectively. Due to the asymmetry of the
cyclometalated phbpy– ligand, the corresponding
[Ru(phbpy)(N–N)(DMSO-κS)]+complexes are chiral.
The exceptional thermal inertness of the Ru–S bond made chiral
resolution of these complexes by thermal ligand exchange impossible.
However, photosubstitution by visible light irradiation in acetonitrile
was possible for three of the five complexes ([1]PF6-[3]PF6). Further thermal coordination
of the chiral sulfoxide (R)-methyl p-tolylsulfoxide to the photoproduct [Ru(phbpy)(phen)(NCMe)]PF6, followed by reverse phase HPLC, led to the separation and
characterization of the two diastereoisomers of [Ru(phbpy)(phen)(MeSO(C7H7))]PF6, thus providing a new photochemical
approach toward the synthesis of chiral cyclometalated ruthenium(II)
complexes. Full photochemical, electrochemical, and frontier orbital
characterization of the cyclometalated complexes [1]PF6-[5]PF6 was performed to explain why
[4]PF6 and [5]PF6 are
photochemically inert while [1]PF6-[3]PF6 perform selective photosubstitution
Cyanopivaloyl Ester in the Automated Solid-Phase Synthesis of Oligorhamnans
No full textBio-organic Synthesi
Photochemical Resolution of a Thermally Inert Cyclometalated Ru(phbpy)(N–N)(Sulfoxide)<sup>+</sup> Complex
No full textIn
this work a photosubstitution strategy is presented that can
be used for the isolation of chiral organometallic complexes. A series
of five cyclometalated complexes Ru(phbpy)(N−N)(DMSO-κS)](PF6) ([1]PF6-[5]PF6) were synthesized and characterized, where Hphbpy = 6′-phenyl-2,2′-bipyridyl,
and N–N = bpy (2,2′-bipyridine), phen (1,10-phenanthroline),
dpq (pyrazino[2,3-f][1,10]phenanthroline), dppz (dipyrido[3,2-a:2′,3′-c]phenazine, or dppn
(benzo[i]dipyrido[3,2-a,2′,3′-c]phenazine), respectively. Due to the asymmetry of the
cyclometalated phbpy– ligand, the corresponding
[Ru(phbpy)(N–N)(DMSO-κS)]+complexes are chiral.
The exceptional thermal inertness of the Ru–S bond made chiral
resolution of these complexes by thermal ligand exchange impossible.
However, photosubstitution by visible light irradiation in acetonitrile
was possible for three of the five complexes ([1]PF6-[3]PF6). Further thermal coordination
of the chiral sulfoxide (R)-methyl p-tolylsulfoxide to the photoproduct [Ru(phbpy)(phen)(NCMe)]PF6, followed by reverse phase HPLC, led to the separation and
characterization of the two diastereoisomers of [Ru(phbpy)(phen)(MeSO(C7H7))]PF6, thus providing a new photochemical
approach toward the synthesis of chiral cyclometalated ruthenium(II)
complexes. Full photochemical, electrochemical, and frontier orbital
characterization of the cyclometalated complexes [1]PF6-[5]PF6 was performed to explain why
[4]PF6 and [5]PF6 are
photochemically inert while [1]PF6-[3]PF6 perform selective photosubstitution
Controlling Multivalent Binding through Surface Chemistry: Model Study on Streptavidin
No full textAlthough multivalent
binding to surfaces is an important tool in
nanotechnology, quantitative information about the residual valency
and orientation of surface-bound molecules is missing. To address
these questions, we study streptavidin (SAv) binding to commonly used
biotinylated surfaces such as supported lipid bilayers (SLBs) and
self-assembled monolayers (SAMs). Stability and kinetics of SAv binding
are characterized by quartz crystal microbalance with dissipation
monitoring, while the residual valency of immobilized SAv is quantified
using spectroscopic ellipsometry by monitoring binding of biotinylated
probes. Purpose-designed SAv constructs having controlled valencies
(mono-, di-, trivalent in terms of biotin-binding sites) are studied
to rationalize the results obtained on regular (tetravalent) SAv.
We find that divalent interaction of SAv with biotinylated surfaces
is a strict requirement for stable immobilization, while monovalent
attachment is reversible and, in the case of SLBs, leads to the extraction
of biotinylated lipids from the bilayer. The surface density and lateral
mobility of biotin, and the SAv surface coverage are all found to
influence the average orientation and residual valency of SAv on a
biotinylated surface. We demonstrate how the residual valency can
be adjusted to one or two biotin binding sites per immobilized SAv
by choosing appropriate surface chemistry. The obtained results provide
means for the rational design of surface-confined supramolecular architectures
involving specific biointeractions at tunable valency. This knowledge
can be used for the development of well-defined bioactive coatings,
biosensors and biomimetic model systems
Automated Solid-Phase Synthesis of Hyaluronan Oligosaccharides
No full textWell-defined fragments of hyaluronic acid (HA) have been obtained through a fully automated solid-phase oligosaccharide synthesis. Disaccharide building blocks, featuring a disarmed glucuronic acid donor moiety and a di-tert-butylsilylidene-protected glucosamine part, were used in the rapid and efficient assembly of HA fragments up to the pentadecamer level, equipped with a conjugation-ready anomeric allyl function
