Novel Cross-linkers and Pharmacological Chaperones Inspired by In Vivo Protein Modifications

This seminar will address three topics. 1: Protein PTMs that cause or contribute to neurodegenerative disease. 2: Protein PTMs that ameliorate neurodegenerative disease. 3: Cyclic thiosulfinate cross-linkers. These highly tunable S-cross-linkers avoid the toxic dead-end modifications created by previous cross-linkers, making safe in vivo cross-linking possible. Applications of this novel, click-type cross-linking reaction include: protecting proteins from disease-associated unfolding; rescuing failed attempts at disulfide trapping; stabilizing quaternary structure; a general tool for cross-linking MS; and creating synthetic polymers. Disease-associated applications include ALS-associated mutations of SOD1 and Parkinson-associated mutations of DJ-1.