Special Issue "Synthesis and Applications of Oligonucleotide Conjugates"
Deadline for manuscript submissions: closed (30 April 2017).
Interests: Kinetic studies on chemical models of ribonucleases and ribozymes; Synthesis and application of oligonucleotide conjugates; Pro-drug strategies for phosphoester drugs; Novel approaches for medium scale synthesis of oligonucleotides
Special Issues and Collections in MDPI journals
Conjugates of oligonucleotides bearing unnatural organic structures or constituents of other biopolymers have found an increasing number of applications as research tools for cell biology. The list of conjugate groups aimed at providing the oligonucleotide with some novel property is extensive. Reporter groups, such as fluorescent dyes and spin-labels, allow for sensitive detection of oligonucleotides. Chemically or photochemically reactive groups may enable site selective cleavage of the target sequence or cross-linking with the target. Intercalators stabilize double helices and groove binders may be exploited in their recognition. Oligonucleotides conjugated to chelating groups serve as target specific carriers of metal ions, finding applications both in diagnostics and chemotherapy. Last, but not least, covalent conjugation of oligonucleotides to molecules that expectedly facilitate internalization, targets the conjugate to a specific cell-type or improves the parmacokinetics offers a possible way to combat against the most severe shortcoming of therapeutic oligonucleotides, viz. inefficient cellular uptake and subsequent release from endosomes to cytoplasm. For this purpose, lipid, carbohydrate, peptide, aptamer and small molecule conjugates are used. It may also be possible to control the intracellular traffic of oligonucleotide drugs by conjugation. In many cases, conjugation through a biodegradable linker is desirable, or biodegradable protecting groups are used. The synthesis of oligonucleotide conjugates is challenging. Synthesis on a single solid support is possible, but usually the conventional protocol of oligonucleotide synthesis has to be modified. Alternatively, bio-orthogonal post-synthetic conjugation in solution may be applied. The present Special Issue is aimed at covering new synthetic methodologies of oligonucleotide conjugates, as well as their novel applications.
Prof. Dr. Harri Lönnberg
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