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Stimuli-responsive self-immolative aliphatic polycarbonates (APCs) and polyesters (APEs) have attractive advantages for biomedical and pharmaceutical applications. In the present work, polycondensation of o-nitrobenzyl-protected serinol was explored as a simple route to obtain light-responsive polycarbonate (LrPC) and polyester (LrPE). By exposure to UV light, these polymers decomposed rapidly and completely into oligomers and small molecules, as detected by size exclusion chromatography (SEC), UV/vis, and 1H nuclear magnetic resonance (NMR) spectroscopies. The degradation mechanism of serinol-based APC and APE was investigated with the help of the Boc-protected model APC and APE, showing that the APC underwent intramolecular cyclization, accompanied by intermolecular transcarbamation, and degraded into oxazolidinone and 2-aminopropanol terminated oligourethanes. Different from APC, the degradation process of serinol-based APE has been proven by electrospray ionization time-of-flight mass spectrometry (ESI-ToF-MS) to follow intramolecular cyclization of the functional amine group with the remote ester group, forming a ten-membered cyclic degradation compound. Further processing of the serinol-based polymers was performed by preparation of nanoparticles (NP). With light-responsive characteristics, a drug delivery system could be potentially obtained enabling a controllable drug release. Based on this strategy, a variety of self-immolative polymers responsive to different triggers can be prepared by polycondensation without the limit of ring-opening polymerization and will expand the family of biodegradable polymers.

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Small RNA viruses only have a very limited coding capacity, thus most viral proteins have evolved to fulfill multiple functions. The highly conserved matrix protein 1 (M1) of influenza A viruses is a prime example for such a multifunctional protein, as it acts as a master regulator of virus replication whose different functions have to be tightly regulated. The underlying mechanisms, however, are still incompletely understood. Increasing evidence points towards an involvement of posttranslational modifications in the spatio-temporal regulation of M1 functions. Here, we analyzed the role of M1 tyrosine phosphorylation in genuine infection by using recombinant viruses expressing M1 phosphomutants. Presence of M1 Y132A led to significantly decreased viral replication compared to wildtype and M1 Y10F. Characterization of phosphorylation dynamics by mass spectrometry revealed the presence of Y132 phosphorylation in M1 incorporated into virions that is most likely mediated by membrane-associated Janus kinases late upon infection. Molecular dynamics simulations unraveled a potential phosphorylation-induced exposure of the positively charged linker domain between helices 4 and 5, supposably acting as interaction platform during viral assembly. Consistently, M1 Y132A showed a defect in lipid raft localization due to reduced interaction with viral HA protein resulting in a diminished structural stability of viral progeny and the formation of filamentous particles. Importantly, reduced M1-RNA binding affinity resulted in an inefficient viral genome incorporation and the production of non-infectious virions that interferes with virus pathogenicity in mice. This study advances our understanding of the