Characterization of Octapeptide GAP as a Precise Carrier for an Imaging or Cancer Therapeutic Agent

摘要

The excitatory glutamic acid is a potent neurotransmitter in central nervous system. Glutamic Acid Peptide (GAP) exerts its action via binding to glutamate receptors (GluRs). GAP has been employed as a targeted carrier, which conjugate to an anticancer agent, a chemotherapeutic agent by peptide or ester linkage. Moreover, its acid residue could chelate to radiometallic isotopes such as ~(68)Ga, ~(99m)Tc for imaging or radiotherapeutic application. Previous study reported that a polyglutamate (MW. 20-50k) is not suitable for imaging needs due to high molecular weight. Thus, commercially available poly-L-glutamic acid (MW. 750-5,000) containing 5-33 glutamic acid moieties is an advantage for better quality of imaging. A wide variety of imaging or radiotherapeutic agents could be developed using this technology for example GAP-estradiol [1,2]. However, various ranges of peptide chain in commercially available GAP lead to occasionally difficult explanation of experiment results. Herein, we rationally designed GAP(YCU)-EDL, a model of conjugated GAP-anticancer, to avoid complicated debates by limiting peptide size to eight glutamic acid moieties. The octapeptide GAP-EDL was synthesized and well characterized to serve for an assessment of precise carrier.