Photoprotector and Antioxidant Properties of Histamine-Containing Peptidomimetics in the Photooxidation of Glycyltryptophan

M. A. Babizhayev^1*, E. L. Lozovskaya², E. N. Makareyeva², Yu. A. Lul'kin¹, and I. I. Sapezhinskii²

¹Helmholtz Research Institute of Eye Diseases, ul. Sadovaya-Chernogryazskaya 14/19, Moscow, 103064 Russia

²Emmanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 117977 Russia; fax: (095) 137-4101; E-mail: chembio@glas.apc.org

^* To whom correspondence should be addressed.

Received July 4, 1997; Revision received November 25, 1997

---

The natural imidazole-containing dipeptide carnosine in vitro exhibits several antioxidant properties; however, in vivo its activity is limited due to enzymatic hydrolysis. A family of original histamine-containing peptidomimetics, i.e., carcinine (beta-alanylhistamine), N-acetylcarcinine (N-acetyl-beta-alanylhistamine), and L-prolylhistamine, which exhibit significant resistance to dipeptidases and retain antioxidant activity, was synthesized. The effect of these compounds on chemiluminescence of glycyltryptophan (Gly-Trp) associated with its photooxidation at the wavelengths over 280 nm and oxidation photosensitized by riboflavin and Rose Bengal was studied. It is shown that all three peptidomimetics efficiently react with singlet oxygen with the rate constant 9·10⁷ M^-1·sec^-1, exhibit free-radical scavenging activity in the course of riboflavin-sensitized Gly-Trp oxidation (C_50% = 8-15 mM), and quench the photoexcited triplet states of the molecules. Unlike these peptidomimetics, carnosine does not react with superoxide generated during the photooxidation of Gly-Trp in the used test system. The data demonstrate photoprotector and antioxidant properties of histamine-containing peptidomimetics in the photooxidation of biological molecules.

---

KEY WORDS: antioxidant, photoprotector, carnosine, histamine-containing peptidomimetics, carcinine, beta-alanylhistamine, N-acetylcarcinine, L-prolylhistamine, glycyltryptophan, chemiluminescence, photosensitized chemiluminescence

---