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

Prof. Jeffrey Agar
Prof. Jeffrey Agar
Chemistry and Chemical Biology
Northeastern University
Chemistry Building, Room 400
Departmental Colloquium

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.

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