Natural cationic polymers protein

The polymers tiiat have been mentioned so far consist of electrically neutral molecules in which the atoms are joined by covalent bonds. There exists, thou > among them a group of polyiners which ionize in certain environments (aqueous, as a rule) and therefore are called pcdyelectrolytes. They may occur in nature, for example, proteins are anionic at high pH and cationic at low pH however, they also may be prepared.synthetically. 

Cationic polymers are of particular interest carriers in drug and gene deliveiy because of their ability to promote cellular uptake.This holds also for the delivery of proteins, especially for those that possess an overall anionic charge at pH values above the isoelectric point (p/). These proteins can form soluble, nanosized, polyelectrolyte complexes with natural or synthetic cationic polymers by simply mixing the oppositely charged protein and polymer that self-assemble by electrostatic attraction, as represented in Scheme 14.1. 

This field of sfudy is actually quite old. Interaction and complex formation between natural polymers (proteins) and surfactants (lipids) were recognized early in this century, and much study on mixtures of proteins and synthetic surfactants was carried out in the 1940s and 1950s (1,2). Work on mixtures of synthetic uncharged polymers and ionic surfactants was initiated by Saito in the 1950s and on various (mostly natural) anionic polymers and cationic surfactants by Scott and co-workers at about the same time. For summaries of this early work several reviews are available (3-5). 

Over the last four decades many different polycations have been employed in polyplexes, including natural DNA binding proteins such as histones, the synthetic amino acid polymers such as polylysine, polyornithine, and other cationic polymers such as polyamidoamine dendrimers, polyethylenimines, chitosan, polyphosphoramidates, or poly (dimethylaminoethyl) methacrylates. The use of these and other polymers has been previously reviewed in [7-9,29,30]. The characteristics of polymers which have been previously most commonly used are discussed below (Sect. 3.1), followed by the review of strategies to optimize these polymers (Sect. 3.2) or novel biodegradable polymers (Sect. 3.3). 

A detailed classification of the chemical compounds usually employed was given by (Dubief et al., 2005). The most important of these are organic acids (carboxylic acids and aromatic sulphonic acids), fatty compounds and their derivatives (fatty acids, fatty alcohols, natural triglycerides, natural waxes, fatty esters, oxyethylenated and oxypropy-lenated waxes, partially sulphated fatty alcohols, lanolin and its derivatives, ceramides), vitamins (A, B and E) (see Section 8.6), protein derivatives (extracts or hydrolysates of keratin, collagen and vegetable proteins), silicones (dimethicone and others), cationic surfactants, cationic polymers, amphoteric and betainic polymers. 

In 1991, Luger et al. revealed by X-ray analysis the crystal structure of a natural DNA-histone complex. The X-ray structure shows in atomic detail how the histone protein octamer is assembled and how the base pairs of DNA are organized into a superhelix around it [74]. Since then this protein structure with cationic amino acids on the surface has acted as a model for the rational design of dendritic polymer-based gene vectors to mimic the globular shape of the natural histone complex [75-77]. 

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