Tissue Protecting Antidotes From Anti-Apoptotic Factors of Mycoplasma

摘要

The major goal of the program is identification of novel radioprotectants of Mycoplasma origin. The program consisted of two branches; screening of Mycoplasma strains for anti-apoptotic factors; and testing of predicted candidates for radioprotective activity. Both approaches were successfully implemented and yielded positive results. First, we have found and are currently characterizing a strong anti-apoptotic activity in the lysates of M. arginini. Second, an extremely potent radioprotectant, named CBLB601, structurally related to Mycoplasma lipopeptides was discovered. We have optimized CBLB601 administration regime for reaching maximal radioprotection as well as embarked upon characterization of its toxicological and pharmacological profiles. CBLB601 showed remarkable efficacy, being capable of protecting 100% of treated mice from supralethal 10Gy total body irradiation dose with evident rescuing lymphoid organs. Initial structure-function analysis of CBLB601 led to the understanding that radioprotection is conferred by stimulation of TLR2/TLR6 but not TLR2/TLR1 dimers.