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Antimicrobial peptides have received increased attention due to the increasing prevalence of antibiotic‐resistant bacteria. However, the development of antimicrobial peptides for clinical applications remains a huge challenge. SPA ([D‐rg1, D‐Trp5,7,9, Leu11]SP), an analog of substance P, is a broad‐spectrum neuropeptide antagonist. In this study, we found that SPA could efficiently kill Gram‐positive and Gram‐negative bacteria by membrane disruption, similar to antimicrobial peptides. In addition, SPA showed high killing activity toward bacteria rather than mammalian cells. Our results also demonstrated that SPA could significantly decrease the expression of proinflammatory cytokines and rescue mice from lethal septic shock induced by lipopolysaccharide (LPS). The impressive therapeutic potential of SPA, as indicated in this study, makes it a good template for developing effective antibiotics. Meanwhile, our study provides a new idea for developing multifunctional therapeutic agents to combat bacterial infections. [ABSTRACT FROM AUTHOR]

Hypochlorous acid (HOCl) is widely used in daily production and life because of its green and strongly oxidizing properties. Additionally, as a vital reactive oxygen species (ROS), it is an innate immune system weapon and performs a critical function in many pathophysiology processes. In this paper, a novel water-soluble fluorescent probe, BMH, with excellent performance is designed and synthesized by simple condensation of benzocoumarin and 2-mercaptoethanol. BMH has specific selectivity, excellent sensitivity, ultra-fast response (<3 s), and a wide pH detection range. The fluorescence intensity of BMH has an excellent linear correlation with the concentration of HOCl in the scope of 0–10 μM, and the calculated detection limit (DL) is 2.45 nM. The intramolecular charge transfer (ICT) sensing mechanism of BL has been verified by fluorescence, UV, and MS studies as well as density functional theory (DFT) calculations. Furthermore, BMH can be incorporated into a solid-state visual sensor to detect HOCl conveniently. BMH was applied to detect HOCl-spiked actual water samples and achieved satisfying recovery rates. Also, the low-toxicity BMH can be successfully used to track changes in endogenous/exogenous HOCl in living cells. In short, BL provides a robust and reliable monitoring tool to reveal the biological functions of HOCl and ensure its safe use. [ABSTRACT FROM AUTHOR]

Camptothecin (CPT), a DNA‐toxin drug, exerts anticancer activity by inhibiting topoisomerase I. Targeted delivery of CPT into the cancer cell nucleus is important for enhancing its therapeutic efficiency. In this study, a new type of acid‐activated cell‐penetrating peptide (CPP) with nuclear localization capacity was constructed by conjugating six histidine residues and a hydrophobic peptide sequence, PFVYLI, to the nuclear localization sequence (NLS). Our results indicated that HNLS‐3 displayed significant pH‐dependent cellular uptake efficiency, endosomal escape ability, and nuclear localization activity. More importantly, the HNLS‐3–CPT conjugate showed obviously enhanced cytotoxicity and selectivity compared with CPT. Taken together, our findings provide an effective approach to develop efficient CPPs with both cancer‐ and nucleus‐targeting properties. [ABSTRACT FROM AUTHOR]

Although cell-penetrating peptides (CPPs) has been proven to be efficient transporter for drug delivery, ideal peptide vectors for tumor therapy are still being urgently sought. Peptide antagonists have attracted substantial attention as targeting molecules because of their high tumor accumulation and antitumor activity compared with agonists. SPA, a derivative of substance P, is a potent antagonist that exhibits antitumor activity. Based on the amino acid composition of SPA, we speculate that it can translocate across cell membranes as CPPs do. In this study, our results demonstrated that SPA could enter cells similarly to a CPP. As a vector, SPA could efficiently deliver camptothecin and plasmids into cells. In addition, our results showed that SPA exhibited low toxicity to normal cells and high enzymatic stability. Taken together, our results validated the ability of SPA for efficient drug delivery. More importantly, our study opens a new avenue for designing ideal CPPs based on peptide antagonists. [ABSTRACT FROM AUTHOR]

Obtaining ideal gene delivery vectors is still a major goal in cancer gene therapy. CAMEL, a short hybrid antimicrobial peptide, can kill cancer cells by membrane lysis. In this study, we constructed a series of non-viral vectors by attaching fatty acids with different chain lengths to the N-terminus of CAMEL. Our results showed that the cellular uptake and transfection efficiency of acyl-CAMEL started to significantly increase from a chain length of 12 carbons. C18-CAMEL was screened for gene delivery because it had the highest transfection efficiency. Surprisingly, C18-CAMEL/plasmid complexes displayed strong endosomal escape activity after entering cells via endocytosis. Importantly, C18-CAMEL could deliver p53 plasmids to cancer cells and significantly inhibited cell proliferation by the expression of p53. In addition, the C18-CAMEL/p53 plasmid complexes and the MDM2 inhibitor nutlin-3a showed significantly synergistic anticancer activity against MCF-7 cells expressing wild-type p53. Conclusively, our study demonstrated that conjugation of stearic acid to antimicrobial peptides is a simple and successful approach for constructing efficient and economical non-viral vectors for cancer gene therapy. [ABSTRACT FROM AUTHOR]

The first synthesis of ent -cleistanthane-type diterpenoid spruceanol with significant anticancer activity is described. A chiral pool approach was employed with a linear sequence of 13 steps beginning from readily available and inexpensive andrographolide. The approach features the construction of an aromatic ring with hydroxyl and methyl groups at C-12 and C-13 of the target compound, respectively, via Lewis acid-controlled regioselective Diels-Alder cycloaddition and the regioselective removal of the primary hydroxyl group of the Diels-Alder adduct.