Poly-L-glutamates

Japanese have also shown interest in poly-(L-glutamic acid) for the manufacture of silk-like fibres. 

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. 

Polypeptides form various secondary structures (a-heUx, 3-sheet, etc.), depending on solution pHs. We have investigated end-anchored poly(L-glutamic acid) andpoly(L-lysine) in various secondary structures [11,29,35,36], using the analytical method for the steric force... 

Figure 11a shows a force-distance profile measnred for poly(L-glutamic acid) brushes (2C18PLGA(44)) in water (pH = 3.0, 10 M HNO3) deposited at 40 mN/m from the water subphase at pH = 3.0. The majority of peptides are in the forms of an a-helix (38% determined from the amide I band) and a random coil. Two major regions are clearly seen in... 

Fig. 3. Backscattered Raman (/R + /L) and ROA (/R — /L) spectra of poly-L-lysine in o -helical (top pair) and disordered (second pair) conformations, and of poly-L-glutamic acid in a-helical (third pair) and disordered (bottom pair) conformations in aqueous solution. Reprinted from Barron et al., 2000, Prog. Biophys. Mol. Biol. 73, 1-49, with permission from Elsevier Science.

Positive ROA bands in the range 1297-1312 cm-1 are also characteristic of a-helix. These are observed at 1300 cm-1 in human serum albumin (Fig. 4) and at 1297 cm-1 in a-helical poly-L-lysine (Fig. 3). These additional bands appear to be associated with a-helix in a more hydrophobic environment (Barron etal., 2000). The striking absence of a positive ROA band in the range 1297-1312 cm-1 in a-helical poly-L-glutamic acid would then suggest that only the hydrated form of a-helix is present, possibly due to the shorter side chains relative to poly-L-lysine,... 

More than 36 years ago, the pH-induced cooperative transitions in CD spectra and other physical properties of poly-L-glutamic acid (PGA) and poly-L-lysine (PL) were reported and taken to correspond to a... 

The most common carrier proteins in use today are keyhole limpet hemocyanin (KLH MW 4.5 X 105 to 1.3 X 107), BSA (MW 67,000), aminoethylated (or cationized) BSA (cBSA), thyroglobulin (MW 660,000), ovalbumin (OVA MW 43,000), and various toxoid proteins, including tetanus toxoid and diphtheria toxoid. Other proteins occasionally used include myoglobin, rabbit serum albumin, immunoglobulin molecules (particularly IgG) from bovine or mouse sera, tuberculin purified protein derivative, and synthetic polypeptides such as poly-L-lysine and poly-L-glutamic acid. 

Higashi N, Shosu T, Koga T, Niwa M, Tanigawa T (2006) pH-responsive, self-assembling nanoparticle from a fullerene-tagged poly(L-glutamic acid) and its superoxide dismutase mimetic property. J. Colloid Interface Sci. 298 118-123. 

Figure 3.16. Effects on the fluorescence of anthrylpolyamme 14 on titration by four biological polyanions, o—O, Heparin A—A. poly-L-glutamate — , dsDMA a—A, ssDNA. (Reproduced from Ref. 25.

The heparin and poly-L-glutamate titrations show a markedly different behavior than do the DNA titrations. As polyanion is added, the fluorescence of the an-thrylpolyamine solution decreases until a well-defined minimum is reached. A new emission at 510 nm, which we assign to the anthracene excimer of 14, increases and decreases coincidently with the titrated fluorescence minimum. Likewise, the UV spectrum of 10 fiM 14 with added heparin shows hypochromism that occurs and disappears coincidently with the fluorescence minimum and a 2-nm red shift. We have proposed template-directed excimer formation as the physical basis for these observations. In the absence of heparin, fluorescence of the unassociated probe is observed. As heparin is added, the fluorescence decreases as a result of heparin-directed interaction between probe molecules. Additional heparin permits the fluorophore population to diffuse over the length of the poly anion, thus avoiding excimer formation and yielding a net CHEF. 

Figure 3.18. Effect of pronase on the CHEQ of probe 13 with 50 equivalents of poly-L-glutamate. a, 10 units pronase , 5 units pronase , 1 unit pronase o, no pronase.

In both cases the top layer of these layered polyelectrolyte films contains many ion sites that can bind redox ions by ion exchange vdth the electrolyte solution. Homo polypeptides such as poly(L-lysine) and poly(L-glutamic add) have been employed to form layered polyelectrolyte films with Fe(CN)6 " electrostatically adsorbed onto ammonium sites in poly(lysine) [45]. Modified electrodes with polyelectrolytes mono-layers have also been deposited using the Langmuir-Blodgett technique [46-48]. 

Fe (quaterpy)(OH)2] anchored to poly-L-glutamate or to poly-D-glutamate acts as a catalyst for the oxidation of epinephrine by H202. [Fe(quaterpy)X2] interacts with bio-substrates. [(H20)(quaterpy)Fe —O—Fe (quaterpy)(H20)] + has been prepared as the dihydrate of its perchlorate salt. " ... 

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