DNA-synthetic polymer conjugates

Figure 4 DNA-synthetic polymer conjugates, (a) Incorporating extended aromatic molecules into DNA creates folded stmctures through jT-stacking. (b) Block copolymers consisting of DNA and synthetic polymers can be assembled into micelles via microphase separation of incompatible blocks, (c) A PEG-DNA-brush block copolymer can shape shift between spherical and cylindrical micelles depending on the specific DNA input, (d) Dendritic DNA, created by covalently modifying short DNA strands with dendritic oligoethylene moieties, self-assembles into long-range fibers without the need for sticky-end cohesion.

Vreeland, W. N. et al. Molar mass profiling of synthetic polymers by free-solution capillary electrophoresis of DNA-polymer conjugates. AnaZyficaZ Chemistry 13, 1795-1803 (2001). 

This chapter will introduce polymer systems containing either naturally occurring maaomolecules (polysaccharides, proteins, DNA) or their subunits (bioanalogous molecules, amino acids, short peptides and peptide derivatives, polypeptides, polynucleotides), respectively. The natural building blocks can be connected by covalent bonds or by self-assembly and either can be used alone (see, e.g.. Section 5.4) or in combination with synthetic polymer units (biohybrids). Alternatively the building block itself may be a hybrid of a natural and synthetic molecule (bioconjugate cf. Section 3.5), as, for instance, a PEG-peptide conjugate. 

The subject of this review is complexes of DNA with synthetic cationic polymers and their application in gene delivery [1 ]. Linear, graft, and comb polymers (flexible, i.e., non-conjugated polymers) are its focus. This review is not meant to be exhaustive but to give representative examples of the various types (chemical structure, architecture, etc.) of synthetic cationic polymers or polyampholytes that can be used to complex DNA. Other interesting synthetic architectures such dendrimers [5-7], dendritic structures/polymers [8, 9], and hyperbranched polymers [10-12] will not be addressed because there are numerous recent valuable reports about their complexes with DNA. Natural or partially synthetic polymers such as polysaccharides (chitosan [13], dextran [14,15], etc.) and peptides [16, 17] for DNA complexation or delivery will not be mentioned. 

Scheme 2 Synthetic scheme of the coupling of DNA with polymers at the (a) 5 -end and (b) 3 -end of the DNA (a) deblocking of DMT, (b) coupling of activated CEPA to the 5 -end, and (c) standard synthesis with nucleoside phosphoramidite. Subsequoitly, in radta to obtain the conjugate, cleavage from the solid supprnt is conducted prior to the washing out of the 2-cyanoethyl groups [19] (figure adapted with permission of the Royal Society of Chemistry)...

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