Abstract
Bio-conjugates for Nanoscale Applications is the title of this thesis, which covers three different
projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated
fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives.
Lipidated fluorescent peptides were designed and synthesized as part of two collaboration projects
utilizing peptide conjugates in nanoscale applications to increase understanding of the role peptides
and proteins plays in biological systems.
Ras proteins are membrane bound molecular switches involved in many signaling pathways
important for cell life and death. Ras proteins have been found to be oncogenic activated in 20% of
all cancer tumors. Therefore, understanding the recruitment and regulation of Ras is crucial to develop
new cancer therapeutics. Three fluorescent lipidated tN-Ras peptide mutants were designed and
synthesized for the Stamou group to study the correlation between lipidation pattern of N-Ras and its
recruitment to the membrane as a function of membrane curvature.
For the construction of potential drug delivery systems, two lipidated and fluorescent targeting
peptides and a control sequence were designed and synthesized, to aim for integrin receptors involved
in cardiovascular diseases. The peptides were conjugated to liposomes by the Loft group creating
peptide liposome conjugates aimed at cardiovascular diseases. The potential of these drug delivery
systems were tested and the results gave possibilty for future development.
Mannose binding lectin (MBL) is a lectin involved in the innate immune system detecting pathogens
by recognizing carbohydrate patterns on their surfaces, thereby activating the lectin pathway. A novel
linker able to conjugate five different carbohydrate oximes with a DNA origami scaffold by an azide
alkyne cycloaddition were designed and synthesized for the Kjems group. The Kjems group applied
the linker to construct a DNA based carbohydrate pattern assay for the study of MBLs ability to
recognize carbohydrate patterns.
Oxime bond formation has for many years been an interest in the Jensen group. Therefore, novel Naryl
N-glycosyl O-R carbohydrate oximes were designed and synthesized to study their stability and
reactivity. The results from these experiments intrigued the search for a new rearrangement reaction
to obtain O-R substituted anilines. However, the rearrangement did not succeed.
projects in chemical bio-conjugation research, namely synthesis and applications of: Lipidated
fluorescent peptides, carbohydrate oxime-azide linkers and N-aryl O-R2 oxyamine derivatives.
Lipidated fluorescent peptides were designed and synthesized as part of two collaboration projects
utilizing peptide conjugates in nanoscale applications to increase understanding of the role peptides
and proteins plays in biological systems.
Ras proteins are membrane bound molecular switches involved in many signaling pathways
important for cell life and death. Ras proteins have been found to be oncogenic activated in 20% of
all cancer tumors. Therefore, understanding the recruitment and regulation of Ras is crucial to develop
new cancer therapeutics. Three fluorescent lipidated tN-Ras peptide mutants were designed and
synthesized for the Stamou group to study the correlation between lipidation pattern of N-Ras and its
recruitment to the membrane as a function of membrane curvature.
For the construction of potential drug delivery systems, two lipidated and fluorescent targeting
peptides and a control sequence were designed and synthesized, to aim for integrin receptors involved
in cardiovascular diseases. The peptides were conjugated to liposomes by the Loft group creating
peptide liposome conjugates aimed at cardiovascular diseases. The potential of these drug delivery
systems were tested and the results gave possibilty for future development.
Mannose binding lectin (MBL) is a lectin involved in the innate immune system detecting pathogens
by recognizing carbohydrate patterns on their surfaces, thereby activating the lectin pathway. A novel
linker able to conjugate five different carbohydrate oximes with a DNA origami scaffold by an azide
alkyne cycloaddition were designed and synthesized for the Kjems group. The Kjems group applied
the linker to construct a DNA based carbohydrate pattern assay for the study of MBLs ability to
recognize carbohydrate patterns.
Oxime bond formation has for many years been an interest in the Jensen group. Therefore, novel Naryl
N-glycosyl O-R carbohydrate oximes were designed and synthesized to study their stability and
reactivity. The results from these experiments intrigued the search for a new rearrangement reaction
to obtain O-R substituted anilines. However, the rearrangement did not succeed.
| Original language | English |
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| Publisher | Department of Chemistry, Faculty of Science, University of Copenhagen |
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| Publication status | Published - 2016 |