Lysine blocking

Fig. 1 Vesicle construct formed from poly(L-lysine)-i)-poly(L-leucme) polypeptides where the poly(L-leucine) block corresponds to the a-helical hydrophobic segments and the poly (L-lysine) block corresponds to the random coil hydrophilic segments. Note that this is one specific example and not all vesicle constructs have a-helical and random coil blocks. Moreover, the amphiphilic copolymer can be comprised of either a pure block copolypeptide or a macromolecule consisting of a polypeptide and another type of polymer. Adapted from [20] with permission. Copyright 2010 American Chemical Society...

A related protein, MRP3, has similar structure to this mutated MRP2 and can transport taurocholic acid but mutation of the equivalent residue, leucine 1084, with lysine-blocked transport of taurocholic acid. In cholestasis there is an induction of MRP3 mRNA suggesting that this transporter is active, at least when bile-acid concentrations are raised within the hepatocyte. This transporter function is shown in Figure 2.1. 

Katayose S, Kataoka K. Water-soluble polyion complex associates of DNA and polyfethylene glycol)-poly(L-lysine) block copolymer. Bioconjugate Chem 1997 8 702-707. 

Harada, A., Togawa, H. and Kataoka, K. (2001) Physicochemical properties and nuclease resistance of antisense-oligodeoxynucleotides entrapped in the core of polyion complex micelles composed of poly(ethylene glycol)-poly (L-Lysine) block copolymers. Eur. J. Pharm. Sci., 13, 35—42. 

The synthesis of the branched core of the lipid headgroups [24, 45] proceeds in the same manner as that of multiple antigenic peptides (MAPs) [50, 51 ] or polyethylene glycol-dendritic oligo-lysine block copolymers [52]. It starts from ornithine... 

Fig. 17 The molecular structure of a poly(ethylene oxide)-b-poly(L-lysine) retinoate complex and a sketch of the polymeric backbone with an a-helical poly(L-lysine) block. Reprinted with permission from [153]. Copyright 2000 American Chemical Society...

Poly(amino acid)s (PAAs) have also been used in drug delivery PEO-(l-aspartic acid) block copolymer nano-associates , formed by dialysis from a dimethyl acetamide solution against water, could be loaded with vasopressin. PLA-(L-lysine) block copolymer microcapsules loaded with fluorescently labelled (FITC) dextran showed release profiles dependent on amino acid content. In a nice study, poly(glutamate(OMe)-sarcosine) block copolymer particles were surface-grafted with poly(A-isopropyl acrylamide) (PNIPAAm) to produce a thermally responsive delivery system FITC-dextran release was faster below the lower critical solution temperature (LCST) than above it. PAAs are prepared by ring-opening polymerisation of A-carboxyanhydride amino acid derivatives, as shown in Scheme 1. 

The work of Bunjapamai, Mahoney and Fagerson (21) was the first successful attempt to separate the effects of racemization from crosslinking as measured by vitro digestion. Alkali-treatment of citraconylated (lysine-blocked) or non-blocked casein resulted in racemized only (blocked) or racemlzed and LAL cross-linked (non-blocked) casein. vitro multienzyme digestion of these preparations as well as untreated casein revealed similarly decreased digestibilities for the treated proteins whether crosslinked or not, indicating that the primary cause for reduction of casein digestibility was racemization. 

NAI Naik, S.S., Ray, J.G., and Savin, D.A., Temperature- and pH-responsive self-assembly of poly(propylene oxide)-i-poly(lysine) block copolymers in aqueous solution, Langmuir, 27, 7231, 2011. 

Itaka K, Yamauchi K, Harada A, Nakamura K, Kawaguchi H, Kataoka K (2003) Polyion complex micelles from plasmid DNA and poly(ethylene glycol)-poly(l-lysine) block copolymer as serum-tolerable polyplex system physicochemical properties of micelles relevant to gene transfection efficiency. Biomaterials 24 4495-4506... 

Kataoka K, Ishihara A, Harada A, Miyazaki H (1998) Effect of the secondary structure of poly (L-lysine) segments on the micellizatimi in aqueous milieu of poly(ethylene glycol)- oly (L-lysine) block copolymer partially substituted with a hydrocinnamoyl group at the JV-epsilon-positioiL Macnnnolecules 31 6071-6076... 

Shiraishi K, Kawano K, Maitani Y, Yokoyama M (2010) Polyion complex micelle MRI contrast agents from poly(ethylene glycol)-b-poly(L-lysine) block copolymers having Gd-DOTA preparations and their control of T-l-relaxivities and blood circulation characteristics. J Control Release 148 160-167. doi 10.1016/j.jconrel.2010.08.018... 

Ge et ai, 2011) and short peptide sequences (Castelletto et al., 2010 de Graaf et ai, 2012) can be prepared that can be cleaved by esterases and proteases. Secondly, a double-hydrophUic block polymer can be used that is converted into a polymer amphiphile by masking the hydrophilicity of one of the polymer blocks. For example, this can be done with a PEG-poly(lysine) block polymer. In the presence of adenosine 5 -triphosphate (ATP), a so-called superamphiphUe is formed, in which the poly(lysine) block is rendered hydrophobic due to the association of multiple ATP molecules to the block and the overall amphiphilic block polymer/ATP associate self-assembles into a micelle. Enzymatic digestion of ATP using a phosphatase recovers the hydrophiUc nature of poly(lysine) and destroys the micelle (Wang ef a/., 2010). 

H. Schlaad, H. Kukula, B. Smarsly, M. Antonietti, T. Pakula, Solid-state morphologies of linear and botdebmsh-shaped polyst5oene—poly(Z-L-lysine) block copolymers. Polymer 43, 5321-5328 (2002)... 

Harada, A., Nakanishi, K., Ichimura, S. et al (2009) Spontaneous formation of narrowly-distributed self-assembly from polyamidoamine dendron-poly(L-lysine) block copolymers through helix-coil transition of poly(L-lysine) block. Journal of Polymer Science Part A Polymer Chemistry, 47,1217-1223. 

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