The binding affinity of single stranded DNA (ssDNA) for gold nanoparticle surface is studied in this work. The data indicate that the strength of interaction between ssDNA and Au particle surface is closely related to the particle size, with smaller particles (5 nm) producing the most pronounced effects. From these experimental findings, a single stranded DNA (ssDNA) based method to assimilate 13 and 5 nm gold nanoparticles was developed, and verified by transmission electron microscopy (TEM). / Singapore-MIT Alliance (SMA)

Mass spectrometry has shown its unique potential for studying the structure of proteins. Associated with various specific techniques (H/D exchange, ion mobility, gas-phase spectroscopy, multidimensional mass analysis), it has demonstrated to be an essential tool allowing primary structures to be analyzed and providing a lot of information about high order conformations. This work assesses the capabilities of these emerging mass spectrometry methods, and especially the gas-phase H/D exchange technique, for the structural analysis of nucleic acids. Gas-phase H/D exchange was first used to study single stranded oligonucleotides. The exchange reactions were performed with CD3OD in the collision cell of a 9.4 T FT-ICR MS. In these experimental conditions and in integrating the experimental and theoretical results, gas-phase H/D exchange was shown to be controlled by hydrogen accessibility and not by the chemical nature of the heteroatom bearing the exchangeable hydrogen. This allowed the presence of one structure or several conformers that possess different exchange properties to be detected. Moreover, when several structures were observed, increasing the internal energy of the ions at the entrance of the H/D exchange cell gave access to a qualitative estimation of the relative height of the isomerization barriers compared to the H/D exchange ones. Ion mobility experiments confirmed independently the H/D exchange results. Comparing the ion activation experiments for H/D exchange and for ion mobility revealed that the most compact conformer displays the fastest H/D exchange. This observation showed that H/D exchange and ion mobility provide us with complementary information because accessibility and macromolecule compactness are not univocally associated. Two other methods having independent principles of operations were sequentially combined. The fragmentation of a totally deuterated dinucleotide in exchangeable positions demonstrated the coexistence of several fragmentation channels. The latter were classified according to the involvement of non-labile or labile protons in the fragmentation process. Double resonance experiments were also performed and demonstrated the existence of consecutive fragmentation mechanisms. The involvement of labile, and therefore exchangeable protons in the fragmentation mechanism casts doubt on the use of tandem mass spectrometry to localize incorporated deuteriums in oligonucleotides. Finally, an exploratory work on the gas-phase H/D exchange of non-covalent complexes is presented.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Not available / text

published_or_final_version / Biochemistry / Master / Master of Philosophy

Thesis (Ph. D.)--Northeastern University, 2008. / Title from title page (viewed March 9, 2009) Graduate School of Arts and Sciences, Dept. of Chemistry and Chemical Biology. Includes bibliographical references (p. 192-205).

Thesis (M. Phil.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 106-115).

Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Chemical and Biochemical Engineering." Includes bibliographical references (p. 129-137).

Thesis (Ph. D.)--Duke University, 2007. / Includes bibliographical references.

Includes bibliographical references.