Macrocyclic Peptides Derived from Familial Alzheimer's Disease Mutants Show Charge-Dependent Oligomeric Assembly and Toxicity.

This work probes the role of charge in the oligomeric assembly, toxicity, and membrane destabilization of a series of peptides derived from Aβ and the E22Q and E22K familial mutants. In the mutant Aβ peptides, an acidic residue (E) is replaced with either a neutral or basic residue (Q or K), thus altering the net charge of the peptide. Acetylation at peripheral positions permits modulation of charge of the peptides and allows investigation of the role of charge in their oligomeric assembly, cytotoxicity, and membrane disruption.

Pyrocinchonimides Conjugate to Amine Groups on Proteins via Imide Transfer.

Advances in bioconjugation, the ability to link biomolecules to each other, small molecules, surfaces, and more, can spur the development of advanced materials and therapeutics. We have discovered that pyrocinchonimide, the dimethylated analogue of maleimide, undergoes a surprising transformation with biomolecules. The reaction targets amines and involves an imide transfer, which has not been previously reported for bioconjugation purposes.