Rational design of stapled antimicrobial peptides.

The global increase in antimicrobial drug resistance has dramatically reduced the effectiveness of traditional antibiotics. Structurally diverse antibiotics are urgently needed to combat multiple-resistant bacterial infections. As part of innate immunity, antimicrobial peptides have been recognized as the most promising candidates because they comprise diverse sequences and mechanisms of action and have a relatively low induction rate of resistance. However, because of their low chemical stability, susceptibility to proteases, and high hemolytic effect, their usage is subject to many restrictions. Chemical modifications such as D-amino acid substitution, cyclization, and unnatural amino acid modification have been used to improve the stability of antimicrobial peptides for decades. Among them, a side-chain covalent bridge modification, the so-called stapled peptide, has attracted much attention. The stapled side-chain bridge stabilizes the secondary structure, induces protease resistance, and increases cell penetration and biological activity. Recent progress in computer-aided drug design and artificial intelligence methods has also been used in the design of stapled antimicrobial peptides and has led to the successful discovery of many prospective peptides. This article reviews the possible structure-activity relationships of stapled antimicrobial peptides, the physicochemical properties that influence their activity (such as net charge, hydrophobicity, helicity, and dipole moment), and computer-aided methods of stapled peptide design. Antimicrobial peptides under clinical trial: Pexiganan (NCT01594762, 2012-05-07). Omiganan (NCT02576847, 2015-10-13).

Recent advances in the exonuclease III-assisted target signal amplification strategy for nucleic acid detection.

The detection of nucleic acids has become significantly important in molecular diagnostics, gene therapy, mutation analysis, forensic investigations and biomedical development, and so on. In recent years, exonuclease III (Exo III) as an enzyme in the 3'-5' exonuclease family has evolved as a frequently used technique for signal amplification of low level DNA target detection. Different from the traditional target amplification strategies, the Exo III-assisted amplification strategy has been used for target DNA detection through directly amplifying the amounts of signal reagents. The Exo III-assisted amplification strategy has its unique advantages and characters, because the character of non-specific recognition of Exo III can overcome the limitation of a target-to-probe ratio of 1 : 1 in the traditional nucleic acid hybridization assay and acquire higher sensitivity. In this review, we selectively discuss the recent advances in the Exo III-assisted amplification strategy, including the amplification strategy integrated with nanomaterials, biosensors, hairpin probes and other nucleic acid detection methods. We also discuss the strengths and limitations of each strategy and methods to overcome the limitations.