Introduction

L-Glutamic acid is one of the 20-22 proteinogenic amino acids, and its codons are GAA and GAG. The carboxylate anions and salts of glutamic acid are known as glutamates. L-glutamic acid is a key chemical transmitter of excitatory signals in the nervous system. The termination of glutamatergic transmission occurs via the uptake of glutamate by a family of high-affinity glutamate transporters that utilize the Na+/K+ electrochemical gradient as a driving force[1].

Uses

L-Glutamic acid is converted into L-glutamine by L-glutamine synthetase. L-glutamine biosynthesize purines and pyrimidines by contributing 3- and 9-nitrogen groups of purine bases, 2- amino group of guanine, 3-nitrogen group and amino group of cytosine which are the bases of DNA and RNA. L-Glutamine cannot be synthesized in neoplastic cells due to the lower reactivity of L-glutamine synthetase. Thus, an antagonist of this enzyme can interfere with the metabolic process of L-glutamine and act as an anticancer agent.

Conjugate with drug

Due to the instability of active lactone, the therapeutic efficacy of 20(s)-camptothecin (CPT) is limited in humans. By binding one molecule of a drug via the c-carboxylic acid of each monomeric subunit of poly-(L-glutamic acid) (PGA) it leads to the stability of lactone. Linking CPT to a high molecular weight anionic polymer, PGA, enhances solubility and improves distribution to the tumor through enhanced permeability and retention (EPR effect).

Several studies have indicated that N-(4-hydroxyphenyl)retinamide (4HPR) treatment is associated with the inhibition of angiogenesis and a decreased vascular response in vitro and in vivo. 4HPR was bound to a synthetic polyamino acid, poly(L-glutamic acid) (PG). PG-4HPR was evaluated for its release kinetics and in vitro anti-proliferative and in vivo antitumor activities against ovarian cancer cell lines. It was confirmed that treatments with both 4HPR and PG-4HPR decreased the expression of pre-angiogenic factor VEGF in SKOV3 tumours. In-vivo, PG-4HPR demonstrated significantly enhanced antitumor activities compared to 4HPR in both early treatment and later treatment protocols. Treatments with PG-4HPR suppressed the expression of VEGF and reduced blood flow into the tumour.

Reference

1. Shih IL, Van YT, Shen MH. Biomedical applications of chemically and microbiologically synthesized poly(glutamic acid) and poly(lysine). Mini Rev Med Chem. 2004; 4(2): 179-188.

2. Dutta S, Ray S, Nagarajan K. Glutamic acid as anticancer agent: An overview. Saudi Pharm J. 2013; 21(4): 337-343.