scholarly journals Improved proteolytic stability and potent activity against Leishmania infantum trypanothione reductase of α/β-peptide foldamers conjugated to cell-penetrating peptides

2017 ◽  
Vol 140 ◽  
pp. 615-623 ◽  
Author(s):  
Héctor de Lucio ◽  
Ana María Gamo ◽  
Marta Ruiz-Santaquiteria ◽  
Sonia de Castro ◽  
Pedro A. Sánchez-Murcia ◽  
...  
2021 ◽  
Author(s):  
Carly K. Schissel ◽  
Charlotte E. Farquhar ◽  
Annika B. Malmberg ◽  
Andrei Loas ◽  
Bradley L. Pentelute

AbstractCell-penetrating peptides (CPPs) can cross the cell membrane to enter the cytosol and deliver otherwise non-penetrant macromolecules such as proteins and oligonucleotides. For example, recent clinical trials have shown that a CPP attached to phosphorodiamidate morpholino oligomers (PMO) resulted in higher muscle concentration, increased exon-skipping and dystrophin production relative to another study of the PMO alone in patients of Duchenne muscular dystrophy. Therefore, effective design and study of CPPs could help enhance therapies for difficult-to-treat diseases. So far, the study of CPPs for PMO delivery has been restricted to predominantly canonical L-peptides. We hypothesized that mirror-image D-peptides could have similar PMO delivery activity as well as enhanced proteolytic stability, facilitating their characterization and quantification from biological milieu. We found that several enantiomeric peptide sequences could deliver a PMO-biotin cargo with similar activities, while remaining stable against serum proteolysis. The biotin label allowed for affinity capture of fully intact PMO-peptide conjugates from whole cell and cytosolic lysates. By profiling a mixture of these constructs in cells, we determined their relative intracellular concentrations. When combined with PMO activity, these concentrations provide a new metric for delivery efficiency which may be useful for determining which peptide sequence to pursue in further pre-clinical studies.Abstract Figure


2020 ◽  
Vol 16 ◽  
Author(s):  
Ali Ahmadi ◽  
Hadi Esmaeili Gouvarchin Ghaleh ◽  
Ruhollah Dorostkar ◽  
Mahdieh Farzanehpour ◽  
Masoumeh Bolandian

Abstract:: Cancer is a genetic disease triggered by gene mutations, which control cell growth and their functionality inherited from previous generations. The targeted therapy of some tumors was not especially successful. A host of new techniques can be used to treat aptamer-mediated targeting, cancer immunotherapy, cancer stem cell (CSC) therapy, cell-penetrating peptides (CPPs), hormone therapy, intracellular cancer cell targeting, nanoparticles, and viral therapy. These include chemical-analog conjugation, gene delivery, ligand-receptor-based targeting, prodrug therapies, and triggered release strategies. Virotherapy is a biotechnological technique for turning viruses into therapeutic agents by the reprogramming of viruses to cure diseases. In several tumors, including melanoma, multiple myeloma, bladder cancer, and breast cancer, the oncolytic capacity of oncolytic Coxsackievirus has been studied. The present study aims to assess oncolytic Coxsackievirus and its mechanisms of effect on cancer cells.


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