Conjugation Strategies

Several strategies are possible for the combination of polypeptides with other polymers. Most of the NCA polymerizations allow the use of functionalized initiators as depicted in Fig. 1, the R group of the initiator is part of the resulting polymer chain. Therefore, polymers with corresponding end groups can be used as macroinitiators in the NCA polymerization to generate block copolymers. The polypeptide can be also used as macroinitiator to start controlled radical or other controlled polymerizations to yield block copolymers. Furthermore, preformed polymers can be used for conjugation, for example by click chemistry. 

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Joyce J, Cook J, Chabot D et al (2006) Immunogenicity and protective efficacy of Bacillus anthracis poly-y-D-glutamic acid capsule covalently coupled to a protein carrier using a novel triazine-based conjugation strategy. J Biol Chem 281 4831 -843... 

A third conjugation strategy was developed in which carbohydrate resi-... 

The coupling step between vector and drug moiety may be performed by either chemical or molecular biological approaches (see Chapter 11 for a more detailed discussion on conjugation strategies in drug targeting research). While the options offered by chemical methods... 

Additional factors that could influence the delivery efficiency and possible side effects of PNA-vector chimeras include the physical linkage between the PNA sequence and vector. Below we provide an overview of different conjugation strategies and provide a step-by-step protocol for disulfide bridge formation between PNA and carrier peptide. 

Finally, oligonucleotides have been conjugated to poly-Lys by adding a ribonucleotide at the 3 end of the oligonucleotide [29,32]. Periodate oxidation of the cw-diol function of the ribonucleotide followed by cyanobo-rohydride reductive amination with the amino groups of poly-Lys yields the desired conjugates (strategy c). 

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