Cationic cell-penetrating peptides (CPPs), such as transactivator of transcription (TAT) peptide, have been proposed as effective drug carriers to improve intracellular delivery of biological macromolecules. Amphibian skin-derived Kunitz-type trypsin inhibitors (KTIs), short counterparts of KTIs from plant sources, were found to possess potent serine protease inhibitory activity. However, poor transmembrane permeability of these molecules has largely hindered the study of the full spectrum of their biological actions. As a result, this study aimed to extend the biological activities of amphibian KTIs by their conjugation to cationic CPPs. Herein, a novel peptide (kunitzin-OV) and its phenylalanine-substituted analogue F9-kunitzin-OV (F9-KOV) were evaluated for inhibition of trypsin/chymotrypsin and showed weak antibacterial activity against . As expected, the conjugation to TAT peptide did not increase membrane lysis compared with the original kunitzin-OV, but effectively assisted this complex to enter cells. TAT-kunitzin-OV (TAT-KOV) exhibited a 32-fold increase in antibacterial activity and an enhanced bactericidal rate against . In addition, the conjugation enabled the parent peptides to exhibit antiproliferative activity against cancer cells. Interestingly, TAT-F9-kunitzin-OV (TAT-F9-KOV) showed stronger antiproliferative activity against human breast cancer (MCF-7) and human glioblastoma (U251MG) cell lines, which TAT-KOV did not possess. Moreover, TAT-F9-KOV showed a 20-25-fold increase in antiproliferative capacity against human lung cancer (H157, H460) cell lines compared with TAT-KOV. Therefore, the conjugation of CPPs effectively solves the problem of cell penetration that short KTIs lack and provides evidence for new potential applications for their subsequent development as new antibacterial and anticancer agents.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9501525 | PMC |
http://dx.doi.org/10.3390/pharmaceutics14091805 | DOI Listing |
Int J Biol Macromol
December 2024
Center of Nanoscience, Nanotechnology, and Innovation - CeNano(2)I, Department of Metallurgical and Materials Engineering, Federal University of Minas Gerais, UFMG, Brazil. Electronic address:
Regrettably, glioblastoma multiforme (GBM) remains the deadliest form of brain cancer, where the early diagnosis plays a pivotal role in the patient's therapy and prognosis. Hence, we report for the first time the design, synthesis, and characterization of new hybrid organic-inorganic stimuli-responsive nanoplexes (NPX) for bioimaging and killing brain cancer cells (GBM, U-87). These nanoplexes were built through coupling two nanoconjugates, produced using a facile, sustainable, green aqueous colloidal process ("bottom-up").
View Article and Find Full Text PDFBiomaterials
December 2024
Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA, 01003, USA. Electronic address:
Biofilm-associated infections arising from antibiotic-resistant bacteria pose a critical challenge to global health. We report the generation of a library of cationic conjugated poly(phenylene ethynylene) (PPE) polymers featuring trimethylammonium terminated sidechains with tunable hydrophobicity. Screening of the library identified an amphiphilic polymer with a C hydrophobic spacer as the polymer with the highest antimicrobial efficacy against biofilms in the dark with excellent selectivity.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, 21702, USA.
Targeted payload delivery strategies, such as antibody-drug conjugates (ADCs), have emerged as important therapeutics. Although considerable efforts have been made in the areas of antibody engineering and labeling methodology, improving the overall physicochemical properties of the linker/payload combination remains an important challenge. Here we report an approach to create an intrinsically hydrophilic linker domain.
View Article and Find Full Text PDFJ Agric Food Chem
December 2024
CAS Key Laboratory of Environmental and Applied Microbiology, Environmental Microbiology Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, China.
BcABA3 is an unusual sesquiterpene synthase that lacks the conserved DDxxD and DTE/NSE motifs. Despite this, it can catalyze the conversion of farnesyl diphosphate to 2Z,4E-α-ionylideneethane. We used structure prediction, multiscale simulations, and site-directed mutagenesis experiments to investigate BcABA3 and its catalytic mechanism.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
School of Basic Medical Sciences/School of Medical Humanities, Guizhou Medical University, Guiyang 550025, China.
Porphyrins serve as photosensitizers (PS) in the realm of cancer photodynamic therapy (PDT). Upon excitation by laser light, porphyrins are capable of converting molecular oxygen into highly cytotoxic singlet oxygen (O). However, the rigid π-conjugated structure of porphyrins frequently results in the formation of aggregates in aqueous solutions, which leads to the self-quenching of the excited state.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!