| 1. |
- Fyrner, Timmy, et al.
(författare)
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Derivatization of a bioorthogonal protected trisaccharide linker : towards multimodal tools for chemical biology
- 2012
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Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 23:6, s. 1333-1340
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Tidskriftsartikel (refereegranskat)abstract
- When cross-linking biomolecules to surfaces or to other biomolecules, the use of appropriate spacer molecules is of great importance. Mimicking the naturally occurring spacer molecules will give further insight into their role and function, possibly unveil important issues regarding the importance of the specificity of carbohydrate-based anchor moieties, in e.g., glycoproteins and glycosylphosphatidylinositols. Herein, we present the synthesis of a lactoside-based trisaccharide, potentially suitable as a heterobifunctional bioorthogonal linker molecule whereon valuable chemical handles have been conjugated. An amino-derivative having thiol functionality shows promise as novel SPR-surfaces. Furthermore, the trisaccharide has been conjugated to a cholesterol moiety in combination with a fluorophore which successfully assemble on the cell surface in lipid microdomains, possibly lipid-rafts. Finally, a CuI-catalyzed azide-alkyne cycloaddition reaction (CuAAC) confirms the potential use of oligosaccharides as bioorthogonal linkers in chemical biology.
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| 2. |
- Fyrner, Timmy
(författare)
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Synthesis of Orthogonally Functionalized Oligosaccharides for Self-assembled Monolayers and as Multimodal Tools in Chemical Biology
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis covers different topics in the field of synthetic organic chemistry combined with the field of surface science and glycobiology.First, the text presents a series of orthogonally protected oligosaccharides (tri-, penta-, and heptasaccharides) of varying length and structures, which are synthesized with the aim of developing novel heterobifunctional biocompatible cross-linkers. Successful conjugation with different chemical handles is also described and used to illustrate the potential implementation of defined carbohydrate based compounds have potential use in biosensing applications. The results of incubation experiments using living cells indicate that the linker is incorporated into cell surfaces and enriched in microdomains.Second, synthesis of various saccharide-terminated alkane thiols immobilized on gold surfaces is reported. The protein adsorption and antifouling characteristics of these surfaces were investigated using model proteins and the common fouling organisms, Ulva linza and Balanus amphitrite.Further, oligo(lactose)-based thiols (di-, tetra-, and hexasaccharides) were synthesized and immobilized on gold nanoparticles to investigate how well these rigid, rod-like oligosaccharides can stabilize such nanoparticles for future use in constructing hybrid nanoparticles.Finally, the thesis describes synthesis of a systematic series of oligo(ethylene) glycols possessing either hydrogen- or methyl-terminated groups. Investigation of the fundamental characteristics of self-assembled monolayers, will give important insights into the design of protein repellant surfaces.
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| 3. |
- Fyrner, Timmy, et al.
(författare)
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Synthesis of tri-, penta-, and hepta-saccharides, functionalized with Orthogonally N-Protected Amino residues at the reducing and non-reducing ends
- 2012
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 68:33, s. 6712-6720
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis of four bifunctionalized orthogonally N-protected oligosaccharides derived from lactose and mannose, intended as cross-linking derivatives, is described. The amino sugar at the non-reducing end is derivatized with an N-Boc-protected glycine moiety, and further connected to either a mannose (1→6) disaccharide or (1→3) lactose units (one, two or three) resulting in tri-, penta-, or heptasaccharides. All of the synthesized oligosaccharides have an Nbenzyloxycarbonyl-aminoethyl residue at the reducing end. The fully orthogonal N-Boc/N-Cbz protection group pattern enables further conjugation/derivatization and results in a hydrophilic cross-linking molecule. It was found that the order of the final synthetic steps were crucial to avoid acyl migration. A suitable amide coupling protocol has been applied to introduce the NBoc-protected glycine moiety in alcoholic solvent. The synthesized oligosaccharides will provide a model system to investigate the influence of length, structure and flexibility. The function of the cross-linked substituents thereby provide valuable insights into the role as a spacer molecule.
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| 4. |
- Malysheva, Lyuba, et al.
(författare)
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Spectroscopic Characterization and Modeling of Methyl- and Hydrogen-Terminated Oligo (ethylene glycol) Self-Assembled Monolayers
- 2012
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 116:22, s. 12008-12016
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Tidskriftsartikel (refereegranskat)abstract
- Two series of oligo (ethylene glycol) (OEG) thiol compounds HS-(CH2CH2O)nR with R = CH3, H and n = 5, 6, 7, have been synthesized and used to form self-assembled monolayers (SAMs) on gold. The data from null ellipsometry, infrared reflection-absorption spectroscopy and ab initio calculations of this type of OH- and CH3-terminated OEG SAMs are used to examine the rarely addressed in-SAM orientation of oligo (ethylene glycols) and to provide detailed assignments of infrared bands in the fingerprint and CH-stretching regions. Based on these results, a new spectral band has been observed at 2947 cm-1 and identified by the firstprinciple calculations as localized vibrations that are specific for hydrogen-terminated OEG thiolate SAMs. This band can be used as an indicator of a high crystalline like ordering. It is further more stressed that theory agrees with the experimentally obtained CH-stretching spectra remarkably well if, and only if, the OEG helix axis within studied SAMs is tilted by about 20o with respect to the surface normal.
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