Potent and selective antifungal agents are urgently needed due to the quick increase of serious invasive fungal infections and the limited antifungal drugs available. Microbial metabolites have been a rich source of antimicrobial agents and have inspired the authors to design and obtain potent and selective antifungal agents, poly(DL‐diaminopropionic acid) (PDAP) from the ring‐opening polymerization of β‐amino acid N‐thiocarboxyanhydrides, by mimicking ε‐poly‐lysine. PDAP kills fungal cells by penetrating the fungal cytoplasm, generating reactive oxygen, and inducing fungal apoptosis. The optimal PDAP displays potent antifungal activity with minimum inhibitory concentration as low as 0.4 µg mL−1 against Candida albicans, negligible hemolysis and cytotoxicity, and no susceptibility to antifungal resistance. In addition, PDAP effectively inhibits the formation of fungal biofilms and eradicates the mature biofilms. In vivo studies show that PDAP is safe and effective in treating fungal keratitis, which suggests PDAPs as promising new antifungal agents.

Drug-resistant bacterial infections have caused serious threats to human health and call for effective antibacterial agents that have low propensity to induce antimicrobial resistance. Host defense peptide–mimicking peptides are actively explored, among which poly-β- l -lysine displays potent antibacterial activity but high cytotoxicity due to the helical structure and strong membrane disruption effect. Here, we report an effective strategy to optimize antimicrobial peptides by switching membrane disrupting to membrane penetrating and intracellular targeting by breaking the helical structure using racemic residues. Introducing β-homo-glycine into poly-β-lysine effectively reduces the toxicity of resulting poly-β-peptides and affords the optimal poly-β-peptide, βLys 50 HG 50 , which shows potent antibacterial activity against clinically isolated methicillin-resistant Staphylococcus aureus (MRSA) and MRSA persister cells, excellent biosafety, no antimicrobial resistance, and strong therapeutic potential in both local and systemic MRSA infections. The optimal poly-β-peptide demonstrates strong therapeutic potential and implies the success of our approach as a generalizable strategy in designing promising antibacterial polypeptides.

The functions of implants like medical devices are often compromised by the hostsforeign-body response (FBR). Herein, we report the development of low-FBR materials inspired by serine-rich sericin from silk. Poly-b-homoserine (b-HS) materials consist of the hydrophilic unnatural amino acid b-homoserine.S elf-assembled monolayers (SAMs) of b-HS resist adsorption by diverse proteins,a sw ell as adhesion by cells,platelets,and diverse microbes.Experiments lasting up to 3months revealed that, while implantation with control PEG hydrogels induced obvious inflammatory responses,c ollagen encapsulation, and macrophage accumulation, these responses were minimal with b-HS hydrogels.S trikingly,t he b-HS hydrogels induce angiogenesis in implant-adjacent tissues. Molecular dynamics simulations indicated that the low FBR performance of b-HS results from what we term "dual hydrogen bonding hydration", wherein both the backbone amide groups and the sidechain hydroxyl groups of b-HS undergo hydration.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

A series of amphipathic poly-β-peptides are designed and synthesized for intracellular protein delivery. The poly-β-peptides with higher molecular weight and hydrophobic contents exhibit higher protein loading as well as superior...