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Lysine‐specific peptide and protein modification strategies are widely used to study charge‐related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge‐related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge‐related protein properties, such as liquid‐liquid phase separation behaviour of α‐synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine‐containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins. [ABSTRACT FROM AUTHOR]

Clearance of amyloid β (Aβ) by immunotherapy is one of the fancy methods to treat Alzheimer's disease (AD). However, the failure of some clinical trials suggested that there may be something ignored in the past development of immunotherapy. Pyroglutamate-3 Aβ (Aβ pE3-X ), which was found to be abundant in the patients' brain, has attracted much attention after the report that Aβ pE3-42 could serve as a template to exacerbate the aggregation of Aβ. In addition, Aβ pE3-X could not be recognized by the antibodies targeting the N-terminus of Aβ, suggesting that Aβ pE3-X maybe the ignored one. Indeed, passive immunization targeting Aβ pE3-X has shown some beneficial results, while active immunotherapy has not been extensively studied. In the present study, we designed and synthesized a novel peptide vaccine targeting Aβ pE3-X , which contains Aβ pE3-15 as B cell epitope and P2 as T cell epitope. We showed that this vaccine could induce strong antibody response to Aβ pE3-X . We also showed that prophylactic immunization of AD model mice with our vaccine could reduce Aβ plaques and rescue cognitive decline. This new kind of Aβ vaccine will open up new directions for AD immunotherapy.

A novel noncovalent strategy to construct chemically synthesized vaccines has been designed to trigger a robust immune response and to dramatically improve the efficiency of vaccine preparation. Glycosylated MUC1 tripartite vaccines were constructed through host-guest interactions with cucurbit[8]uril. These vaccines elicited high levels of IgG antibodies that were recognized by transformed cells and induced the secretion of cytokines. The antisera also mediated complement-dependent cytotoxicity. This noncovalent strategy with good suitability, scalability, and feasibility can be applied as a universal strategy for the construction of chemically synthesized vaccines., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)