Lysine synthetic polymers

Historically, after the development of oligopeptide-based vesicles, several groups developed and characterized vesicles using polypeptide hybrid systems consisting of polypeptide and synthetic polymer blocks [17-19]. Soon thereafter, vesicles formed entirely from polypeptides, such as poly(L-lysine)-h-poly(L-leucine) and poly(L-lysine)-h-poly(L-glutamate), were developed [20, 21]. This review will focus on recent developments in the formation of vesicles composed of polypeptide hybrid or polypeptide systems, as well as the potential promise of these systems as effective dmg delivery vehicles. A specific example of a polypeptide-based vesicle is shown in Fig. 1, where the hydrophobic segment is a-helical and the hydrophilic segment is a random coil. 

Synthetic Polymers. Synthetic polymers are versatile and offer promise for both targeting and extracellular-intracellular drug delivery. Of the many soluble synthetic polymers known, the poly(amino acids) [poly(L-lysine), poly(L-aspartic acid), and poly(glutamic acid)], poly(hydroxypropylmethacrylamide) copolymers (polyHPMA), and maleic anhydride copolymers have been investigated extensively, particularly in the treatment of cancers. A brief discussion of these materials is presented. 

Cationic polymer is also frequently examined to increase the potential of a gene drug. Large molecular weight cationic polymers can condense pDNA more efficiently than cationic liposomes. They include poly-L-lysine (PLL), poly-L-omithine, polyethyleneimine (PEI), chitosan, starburst dendrimer and various novel synthetic polymers. These polymers can enhance the cellular uptake of pDNA by nonspecific adsorptive endocytosis. 

Soluble carriers include antibodies and soluble synthetic polymers such as poly(hydroxypropyl methacrylate), poly(lysine), poly(aspartic acid), polyvinylpyrrolidone), poly(N-vinyl-2-pyrrolidone-co-vinylamide) and poly (styrene co-maleic acid/anhydride). 

Polymer-Polymer Interactions Between Nucleic Acid Base - Substituted Poly-I.-Lysine and Other Synthetic Polymers... 

Synthetic polymers of lysine can be produced in a range of molecular weights. Those in the range 30 000-300 000 have been found useful in providing a positive surface charge on glass or plastic (McKeehan Ham, 1976). 

Synthetic polymers containing photochromic units can undergo reversible changes of their physical and chemical characteristics. (For recent reviews, see Refs. 24-26). Recent examples involving photochromic compounds other than spiropyrans are reported in Refs. 27-31. Spiropyran-containing polymers such as polyacrylates have also been prepared and were found to show photoinduced variations of their viscosity.18- 0 The change in the viscosity of the polymers partly reflects the polymer conformation. Thus, spiropyran-attached poly(L-tyro-sine) and poly(L-lysine) were synthesized by Vandewyer and Smets at the University of Louvain in 1970.32 33 No photoresponsiveness was observed however, for these modified peptides. 

Biological molecules do show regularity at the level that is not obtained with synthetic polymers. Protein folding is a perfect example, but it is not yet well understood. Therefore, protein-based 3D drug delivery systems are difficult to design. However, small peptides with amphiphilic structure (e.g., V6K, where six valines form hydrophobic part and lysine is the hydrophilic end group) can assemble... 

Despite the drawbacks of this method, it has been used to prepare a tremendous number of polypeptide hybrid block copolymers (Table 1), and when carefully executed provides reasonably well-defined samples. Synthetic polymer domains have been prepared by addition polymerization of conventional vinyl monomers, such as styrene and butadiene, as well as by ringopening polymerization in the cases of ethylene oxide and e-caprolactone. The generality of this approach allows NCA polymerization off of virtually any primary amine functionality, which was exploited in the preparation of star block copolymers by polymerization of sarcosine NCA from an amine-terminated trimethyleneimine dendritic core [37]. In most examples, the polypeptide domain was based on derivatives of either lysine or glutamate, since these form a-helical polypeptides with good solubility characteristics. These residues are also desirable since, when deprotected, they give polypep-... 

Two older reviews summarize work in this field [124,125]. The following derivatives have been employed as porphyrins Fe(II,III) protoporphyrin-EX (heme, hemin), Fe(II,III) or Co(II) protoporphyrin-IX-diester, chlorophyllins with different metal ions in the core, Fe(II) tetraphenylporphyrin, Mg(II) or Fe(II,III) octaethylporphyrin, Fe(II,III) tetrakis[o-(alkylamido)phenyl]-porphyrin. Polymers with N-donor groups are based on proteins such as poly(L-lysine), poly(L-histidine), poly(Y-benzyl-L-glutamate) or synthetic polymers such as homopolymers and copolymers with vinylpyridine, iV-vinylimidazole or ethyleneimine. 

Poly(L-lysine) (PLL) is a biodegradable synthetic polymer obtained from polymerization of the N-carboxyanhydride of lysine, having protonable amine groups on the lysine moiety (see Figure ll.lE). 

These polymers consist of a synthetic polymer backbone onto which amino acids or peptides are grafted as side chains. Examples of materials with amino acids as side chains have been found to exhibit polyelectrolytic and metal complexation behaviour. Such systems include polymethacrylamides with glycylglycine and phenylalanine (Methenitis, 1994), as well as alanine, aspartic acid, asparagine, glutamic acid, and lysine (Morcellet-Sauvage, 1981 Morcellet, 1982 Lekchiri, 1987). 

To understand how measurement of optical activity can provide us an idea about the conformation of a maciomolecule, we will consider an example of synthetic polypeptide pofy-L-lysine. This synthetic polymer is readily soluble in water at pH 5.7. At this pH the e-amino groups are protonated. Consequently the pol)mier can exist in a variety of conformations. The potymer may then be thought as existing in a remdom coil state in solution. Observe the CD (Figure 9.4(B)) and ORD (Figure 9.4(A)) of this random eoU (only CD is discussed observe, however, that wherever extinction is maximum for CD, ORD is zero). There is a weak positive circular dichroism at 217 nm and a strong negative eircular dichrolsm at 197 nm. 

Figure 1.3 Bioconjugation of synthetic polymers by targeting primaiy amines within biomacromolecules resulting in amide bond formation at the N-terminus or the lysine side chain (a) iV-hydro>ysuccinimidyl (NHS) activated ester,(b) pentafluorophenyl-activated ester. ...

Bellomo and co-workers prepared a new type of synthetic vesicle with a high degree of architectural control made of amphiphilic block copolypeptides (Bellomo et al., 2004). The hydrophUic block was made of lysine, augmented with a few water-soluble ethylene glycol units, and the hydro-phobic block was constituted by leucine peptide. The synthetic polymer forms a supramolecular structure highly sensitive to environmental signals... 

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