A fourth generation poly-lysine dendritic nanocarrier (P4LDN)-based targeted chemotherapy for breast cancer is attempted by incorporating an epidermal growth factor receptor (EGFR)-specific short peptide E2 (ARSHVGYTGAR) and the drug methotrexate (MTX) into a nanocarrier system. The drug is incorporated into the nanocarrier using a cathepsin B cleavable spacer: glycine–phenylalanine–leucine–glycine (GFLG). The in vitro analysis of the time-dependent drug release, binding and internalization ability, and the cytotoxic nature showed that this drug delivery system (DDS) is highly effective. The efficacy analysis using non-obese diabetic/severe combined immunodeficiency (NOD-SCID) mice also showed that compared to the control group, the DDS can effectively reduce tumor volume. The mice that received the DDS appeared to gain weight more rapidly than the free drug, which suggests that the dendrimer is more easily tolerated by mice than the free drug.
A twenty-two-residue peptide Brevinin1 Clinotarsus curtipus-3 (B1CTcu3), identified from the skin secretion of frog Clinotarsus curtipes of the Western Ghats, exhibited a broad range of antibacterial activity against Gram-negative and Gram-positive bacteria, including the methicillin-resistant Staphylococcus aureus (MRSA). It showed anti-biofilm activity even at subminimum inhibitory concentration (sub-MIC) against Pseudomonas aeruginosa and Staphylococcus aureus. Analysis of the scanning electron microscopic (SEM) images, confocal images, flow cytometric data and the effect of salt concentration on antibacterial potency suggests that the killing action of the peptide is through the membranolytic process. Single channel electric recording confirmed that the peptide elicited pores on the bacterial cell membrane as it induces a heterogeneous channel in the lipid bilayer. It also showed cytotoxicity against MDA-MB-231 breast cancer cell with IC 50 of 25 μM. B1CTcu3 peptide could serve as the template for next-generation antibacterial agents, particularly against antibiotic resistant pathogenic bacteria.
The CCR5 antagonism represents a promising pharmacological strategy for therapeutic intervention, as it plays a significant role in reducing the severity and progression of a wide range of pathological conditions. Here we designed and generated peptide ligands targeting the chemokine receptor; CCR5 that were derived from the critical interaction sites of the V3 crown domain of envelope protein glycoprotein gp120 (TRKSIHIGPGRAFYTTGEI) of HIV-1 using computational biology approach and the peptide sequence corresponding to this region was taken as the template peptide, designated as TMP-1. The peptide variants were synthesized by employing Fmoc chemistry using polymer support and were labelled with Rhodamine B to study their interaction with the CCR5 receptor expressed on various cells. TMP-1 and TMP-2 were selected as the high-affinity ligands from in vitro receptor binding assays. Specific receptor binding experiments in activated peripheral blood mononuclear cells (PBMCs) and HOS.CCR5 cells indicated that TMP-1 and TMP-2 had significant CCR5 specificity. Further, the functional analysis of TMP peptides using chemotactic migration assay showed that both peptides did not mediate the migration of responsive cells. Thus TMP-1 and TMP-2 represent promising CCR5 targeting peptide candidates.
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