Michael Chr. Wamberg

Intercalating Nucleic Acids: The Influence of Linker Length and Intercalator Type on Their Duplex Stabilities

Six new examples of intercalating nucleic acids were synthesized in order to evaluate the dependence of the length of the linker between oligo and intercalator on the thermal stability of their corresponding duplexes and triplexes. †In honour and celebration of the 70th birthday of Professor Leroy B. Townsend. ††A research center funded by The National Danish Research Foundation for studies on nucleic acid chemical biology.

Pyrene intercalating nucleic acids with a carbon linker.

We have synthesized a carbon linker analogue of INA (oligonucleotides containing insertions of 1-O-(1-pyrenylmethyl)glycerol). Thermal stability studies showed an increase in melting temperature in favor of the carbon linker analogue. We also synthesized a carbon linker analogue with two pyrenes geminally attached. Fluorescence studies of this intercalating nucleic acid with the pyrene moieties inserted as a bulge showed formation of an excimer band. When a mismatch was introduced at the site of the intercalator, an excimer band was formed for the destabilized duplexes whereas an exciplex band was observed when the stability of the duplex was retained.

Bottom–Up Protocell Design: Gaining Insights in the Emergence of Complex Functions

All contemporary living cells are a collection of self-assembled molecular elements that by themselves are non-living but through the creation of a network exhibit the emergent properties of self-maintenance, self-reproduction, and evolution. Protocells are chemical systems that should mimic cell behavior and their emergent properties through the interactions of their components. For a functional protocell designed bottom-up, three fundamental elements are required: a compartment, a reaction network, and an information system. Even if the functions of protocell components are very simplified compared to those of modern cells, realizing a system with true inter-connection and inter-dependence of all the functions should lead to emergent properties. However, none of the currently studied systems have yet reached the threshold level necessary to be considered alive. This chapter will discuss the on-going research that aims at creating artificial cells assembled from a collection of smaller components, i.e., protocell systems from bottom-up designs.

Synthesis of Lipophilic Guanine N-9 Derivatives: Membrane Anchoring of Nucleobases Tailored to Fatty Acid Vesicles

Covalent or noncovalent surface functionalization of soft-matter structures is an important tool for tailoring their function and stability. Functionalized surfaces and nanoparticles have found numerous applications in drug delivery and diagnostics, and new functionalization chemistry is continuously being developed in the discipline of bottom-up systems chemistry. The association of polar functional molecules, e.g., molecular recognition agents, with soft-matter structures can be achieved by derivatization with alkyl chains, allowing noncovalent anchoring into amphiphilic membranes. We report the synthesis of five new guanine-N9 derivatives bearing alkyl chains with different attachment chemistries, exploiting a synthesis pathway that allows a flexible choice of hydrophobic anchor moiety. In this study, these guanine derivatives were functionalized with C10 chains for insertion into decanoic acid bilayer structures, in which both alkyl chain length and attachment chemistry determined their interaction with the membrane. Incubation of these guanine conjugates, as solids, with a decanoic acid vesicle suspension, showed that ether- and triazole-linked C10 anchors yielded an increased partitioning of the guanine derivative into the membranous phase compared to directly N-9-linked saturated alkyl anchors. Decanoic acid vesicle membranes could be loaded with up to 5.5 mol % guanine derivative, a 6-fold increase over previous limits. Thus, anchor chemistries exhibiting favorable interactions with a bilayers hydrophilic surface can significantly increase the degree of structure functionalization.