Polylysine chains

This method represents one of the first attempts towards macromolecular agents.121-123 As many as 60-90 [Gd(DTPA)]2- or [Gd(DOTA)] chelates were first linked to a polylysine chain, then covalently conjugated to a HSA molecule.124 The increase in relaxivity per Gd, as compared with the monomeric chelate, was remarkable (two- to threefold), though far from optimal. However, the development of these albumin conjugates was abandoned at an early stage, since their synthesis is not easily controlled, and there are also toxicity concerns due to the retention of gadolinium observed in the bones and liver.125... 

The most commonly used polymers are the cationic lipids and polylysine chains (Figure 14.8). Cationic lipids can aggregate in aqueous-based systems to form vesicles/liposomes, which in turn... 

The behaviour of copolymers SK is typical for the behaviour of copolymers with a hydrophobic polyvinyl block and a hydrophilic polypeptide block. They exhibit mesophases in water for water concentration ranging from 0 to 50% and the structure of the mesophases is lamellar23. The special feature of this lamellar structure consists in the conformation of the polylysine chains which are roughly to 15% in a 0-chain conformation, to 35% in an a-helix conformation and to 50% in a coiled conformation23, so that the hydrophilic block of such amphipatic copolymers has the same type of conformation as the hydrophilic part of the membrane proteins. 

Fig. 16 (a) Representation of a block copolypeptide chain and (b) proposed packing of block copolypeptides into twisted fibrillar tapes. Polylysine chains were omitted from the fibril drawing for clarity. Reproduced from [105] with permission of The Royal Society of Chemistry... 

GOx was genetically modified so that a polylysine chain was appended at the C terminus of the enzyme mutant Coupling of ferrocenyl groups was performed by reaction of 6 and EDAC in the presence of 2 M urea, and the resulting enzyme was shown to retain 90% of enzymatic activity as compared with native GOx [22]. 

Macromolecules bearing reactive groups in the repeat units along their chains are capable of multiple interaction with the matrix. As early as 1973, Wilchek prepared Sepharose-based supports chemically modified by chemisorbed polylysine and polyvinylamine [41]. The leakage of dyes covalently bonded to these supports was reduced remarkably as compared to non-modified Sepharose activated by cyanogen bromide. Thus, stable and high capacity affinity adsorbents could be prepared by the introduction of macromolecular spacers between a matrix and a biospecific ligand. 

Ziady AG, Ferkol T, Dawson DV, Perlmutter DH, Davis PB (1999) Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo. J Biol Chem 274 4908 1916... 

Figure 11.19 (a) Structure of a hydrophilic fifth-generation poly(propylene imine) dendron containing a focal hydrophobic polystyrene block, (b) Structure of a fourth-generation r-buty-loxycarbonyl (Boc)-protected polylysine dendron having a focal poly(ethylene glycol) chain. 

SUVs have also been stabilized by coating their outer surfaces with chitin [328], polylysine [329-332], polyelectrolytes [333], and polysaccharides [334]. Advantage has also been taken of electrostatic interactions to attract oppositely charged polyelectrolytes to outer SUV surfaces and subsequently polymerize them in situ [335-339]. These systems have been referred to as liposomes in a net [72]. A particularly telling example is the attachment of a two-dimensional polymeric network either to the inner or to the outer surfaces of SUVs by ion exchanging the vesicle counterions with oppositely charged polymerizable short-chain counterions and their subsequent polymerization (Fig. 42) [340-342]. 

Thus one might expect flexible, water-soluble synthetic polymers with suitable side chains to show strong affinities for small molecules. In the course of 20 years we examined the binding ability of polyvinylpyrrolidone, polyvinylpyridine, polylysine, polyacrylamide, polyisopro-pylacrylamide, polyvinylimidazole, polyvinylmethyloxazolidinone,... 

Other investigators have also studied similar synthetic polymers.11-17 In our experience no water-soluble polymer binds small molecules with an avidity comparable to serum albumin. A comparison of the latter with two of the best-binding polymers18 is shown in Fig. 1. Neither polymer binds as strongly as serum albumin. Despite its large cationic charge and many apolar (—CH2—CH2—CH2—CH2—) side chains, polylysine shows very weak affinity for anions. Polyvinylpyrrolidone is more effective but not impressive. 

Medley, Q.W. Bagshaw, W.L. Truong, T. Cote, G.P. Dictyostelium myosin II heavy-chain kinase A is activated by heparin, DNA and acidic phospholipids and inhibited by polylysine, polyarginine and histones. Biochim. Biophys. Acta, 1175, 7-12 (1992)... 

Maruyama, A., Watanabe, H., Ferdous, A., Katoh, M, Ishihara, T. and Akaike, T. (1998) Characterization of interpolyelectrolyte complexes between double- stranded DNA and polylysine comb-type copolymers having hydrophilic side chains. Biocmjug. Chem., 9, 292-299. 

The lipid-core peptide (LCP) system (Toth et al. 1993 Moyle et al. 2003) (Fig. 11.3) is a delivery system which conjugates synthetic lipoamino acids (a-amino acids with long alkyl side chains) through a polylysine MAP system (or a carbohydrate) (McGeary et al. 2001, 2002) to multiple copies of one or several different peptide antigens. The LCP system induces similar immune responses when LCP-based vaccines are co-administered with conventional adjuvants and represents a promising system for mucosal vaccine development. 

Thus one might expect flexible, water-soluble synthetic polymers with suitable side chains to show affinities for small molecules. We have examined, over several decades, the binding ability of poly(vinylpyrrolidone), polyvinylpyridine, polylysine, polyacrylamide, poly(isopropylacrylamide), poly(vinylimidazole), poly(vinylmethyloxazolidi-none), poly(vinylmethyloxazolidinone-vinylimidazole), poly(vinylpyrrolidone-vinyli-midazole), poly(vinylpyrrolidone-vinyl alcohol), poly(vinylpyrrolidone-maleic anhydride), poly(vinylmethyloxazolidinone-maleic anhydride), and poly(2-methylami-noethyl methylacrylate-methacrylic acid). Other investigators have studied similar synthetic polymers [5-12], In our experience no water-soluble polymer binds small molecules with an avidity comparable to serum albumin. 

The liquid phase synthesis on PEG has also been used for the conformational analysis of collagen-like sequences by CD studies 237). The attachment to PEG has also permitted the CD spectral delineation of the specific interactions between the polypeptide chains and sidechain groups 238,239). Thus, Anzinger et al. observed that onset of local ordered structures in the mesogenic side chains of polylysine blocks attached to PEG leads to significant, specific alteration in the backbone conformations of the peptide chain 239). 

Gougeon, R.D., Reinholdt, M., Delmotte, L., Miehe-Brendle, J., Chezeau, J.M., Le Dred, R., Marchal, R., Jeandet, P. (2002). Direct observation of polylysine side-chain interaction with smectites interlayer surfaces through H- Al heteronuclear correlation NMR spectroscopy, Langmuir, 18, 3396-3398. 

Gougeon, R.D., Reinholdt, M., Delmotte, L., Miehe-Brendle, J., Chezeau, J.M., Le Dred, R., Mar-chal, R., Jeandet, P. (2002). Direct observation of polylysine side-chain interaction with smectites interlayer surfaces through H- A1 heteronuclear correlation NMR spectroscopy. Langmuir, the American Chemical Society Journal of Surfaces and Colloids, 18, 3396-3398 Gougeon, R.D., Soulard, M., Reinholdt, M., Miehe-Brendle, J., Chezeau, J.M., Le Dred, R., Mar-chal, R., Jeandet, P. (2003). Polypeptide adsorption onto a synthetic montmoriUonite A combined solid-state NMR, X-ray diffraction, thermal analysis and N2 adsorption study. Eur. J. Inorg. Chem., 2003, 1366-1372... 

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