Poly-L-aspartic acid

Poly-L-lysine and polyglutamic acid Poly-L-aspartic acid Polypeptide-mustard conjugates HPMA... 

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. 

POLY(AMINO acids). Both anionic [e.g., poly(L-aspartic acid) and poly(glutamic acid)] and cationic [e.g., poly[L-lysine)] poly(amino acids) have been suggested as potential drug carriers. Poly(L-lysine) is a homopolymer cosisting of repeating units of L-lysine. It exhibits some affinity for cancer cells and possesses antimicrobial and antiviral properties. It also shows... 

A Berger, E Katchalski. Poly-L-aspartic acid, (saponification). J Am Chem Soc 73, 4084, 1951. 

Leukemia P388 has also been used as a primary screen to detect the antitumor activity of macromolecular conjugates. For example, Ohya et al. [213] used P388 to determine the antitumor activities of polygalactosamine immobilized 5-fluoruracil, and Zunino et al. [214] of a poly-L-aspartic acid-daunomycin conjugate. 

B16 melanoma, Walker sarcoma, and M5076 forming liver metastasis have been used in the preclinical evaluation of HPMA copolymer-adriamydn conjugates [36]. Other tumors useful for secondary screening are MS-2 sarcoma, NMU-1 murine lung adenocarcinoma, and murine adenocarcinoma Colon 26. These have been used by Zunino et al. [147] to determine the activity of poly (carboxylic acid) immobilized anthracyclines. Mice inoculated intramuscularly with Lewis lung carcinoma have been used by Pratesi et al. [215] to assess the effect of a poly-L-aspartic acid/doxorubicin conjugate. 

Typical photoresponsive polypeptides exhibiting a helix-helix transition upon photoirradiation are shown in Fig. 1. These polypeptides are composed of l-aspartates as the amino acid component. The poly(l-aspartic acid esters) are the most thoroughly investigated polypeptides with respect to their ordered structures... 

On the basis of these observations, Ueno et al. designed and synthesized a series of poly(L-aspartic acid ester)-containing azobenzene pendants as the pho-... 

PAA poly-L-aspartic acid RANTES regulated on activation, normal T-cell ex-... 

Poly(L-aspartic acid) Hydrolyzable targeting carrier for cancer... 

One relatively recent example is the cyanobacterial nitrogen reserve cyanophy-cin (multi-L-arginyl-poly-L-aspartic acid). This polymer is of interest because the oligo-arginyl polyaspartic acid may function as a biodegradable polyelectrolyte in selected applications. This polymer is synthesized in vivo by the enzyme... 

Berg, H., Ziegler, K., Piotukh, K., Baier, K., Lockau, W., and Volkmer-Engert, R. (2000) Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin) Mechanism of the cyanophycin synthetase reaction studied with synthetic primers. Eur.J. Biochem., 267, 5561-5570. 

The third mechanism is represented by nonmodular one-step peptide synthesis. Enzymes belonging to this group catalyze the biosynthesis of poly(amino acids). Naturally occurring poly(amino acids) comprise cyanophy-cin [multi-L-arginyl-poly-(L-aspartic acid) cyanophycin granule polypeptide, (CGP)], (poly-(e-lysine) (PL), and poly-(y-glutamate) (PGA). As a consequence of non-ribosomal biosynthesis these peptides reveal a polydisperse mass distribution. 

Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin). 

Simon, R.D. (1976) The biosynthesis of multi-l-arginyl-poly(L-aspartic acid) in the filamentous cyanobacterium Anabaena cylindrica. Biochim. Biophys. Acta, 422, 407-418. 

Zunino, F., GiuUiani, F., Savi, G., Dasdia, T. and Gambetta, R. (1982) Anti-tumour activity of daunorubicin linked to poly-L-aspartic acid. J. Pharmacol. Exp. Ther. 30 465-469. 

Aoyagi T, Sugi K, Sakurai Y, Okano T, Kataoka K. Peptide drug carrier studies on incorporation of vasopressin into nano-associates comprising poly(ethylene glycol)-poly(L-aspartic acid) block copolymer. Colloid Surf B 1999 16 237-242. 

Peptides are known to show some specificity toward metal binding, as was shown by titration experiments nsing H-NMR [7,8], potentiometry [9], luminescence measnrements [10], infrared (IR), circular dichroism (CD), and ultraviolet (UV spectroscopies [11]. Poly-L-aspartic acid binds to metals such as Eu, Ce, La +, Cu ", and Pb ", and acts as a corrosion inhibitor for steel and iron. This property has been ascribed to the carboxylate side chain of aspartic acid [12,13]. 

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