BACKGROUND Aberrant expression of the RON receptor tyrosine kinase, a member of the MET proto-oncogene family, in breast cancer and non-small cell lung cancer (NSCLC) has therapeutic implication. Here we evaluated the efficacy of a novel anti-RON antibody-drug maytansinoid conjugate Zt/g4-DM1 for treatment of breast and NSCLC xenograft tumors in mouse models and explored a treatment strategy by...

G-quadruplex (G4)-interactive small molecules have a wide range of potential applications, not only as drugs, but also sensors quadruplex structures. The purpose this work is the synthesis analogues bis-methylquinolinium-pyridine-2,6-dicarboxamide G4 ligand 360A, to identify relevant structure–activity relationships apply design other G4-interactive bearing bis-quinoline or bis-isoquinoline moi...

The hemagglutinin-neuraminidase (HN) protein of Newcastle disease virus (NDV) is an important determinant of its virulence. We investigated the role of each of the four functional N-linked glycosylation sites (G1 to G4) of the HN glycoprotein of NDV on its pathogenicity. The N-linked glycosylation sites G1 to G4 at residues 119, 341, 433, and 481, respectively, of a moderately pathogenic NDV st...

The livestock sector in Pakistan occupies a unique position in the national agenda of economic development. The current study was conducted to evaluate a heat stress mitigation strategy through different feeding times on the performance i.e. milk yield, milk composition and physiochemical properties of milk in dairy cattle during the summer season. Twenty Holstein Friesian cows (HF) were random...

A red-light triggered G-quadruplex photoalkylation procedure is reported, based on a bi-molecular approach involving the irradiation of G4-binding photosensitizer in presence furan-containing G4-ligand.

Expression of GLUT4 in fast-twitch skeletal muscle fibers of GLUT4 null mice (G4-MO) normalized glucose uptake in muscle and restored peripheral insulin sensitivity. GLUT4 null mice exhibit altered carbohydrate and lipid metabolism in liver and skeletal muscle. To test the hypothesis that increased glucose utilization by G4-MO muscle would normalize the changes seen in the GLUT4 null liver, ser...

Quadruplex (G4) forming sequences in telomeric DNA and c-myc promoter regions of human DNA are associated with tumorogenesis. Ligands that can facilitate or stabilize the formation and increase the stabilization of G4 can prevent tumor cell proliferation and have been regarded as potential anti-cancer drugs. In the present study, steady state and time-resolved fluorescence measurements provide ...

Previous evidence indicates that telomeres resemble common fragile sites and present a challenge for DNA replication. The precise impediments to replication fork progression at telomeric TTAGGG repeats are unknown, but are proposed to include G-quadruplexes (G4) on the G-rich strand. Here we examined DNA synthesis and progression by the replicative DNA polymerase δ/proliferating cell nuclear an...

Multiwalled carbon nanotubes (MWCNTs)amphiphilic poly(amidoamine) (PAMAM) dendrimers (APAMAM) based hybrids were developed through individual functionalization of PAMAM with generation 4 (G4) and generation 5 APAMAM (G5) on MWCNTs. The two hybrids were used as matrices and deposited with silver (Ag) nanoparticles (NPs) to develop another two types of new MWCNT based hybrids viz., MWCNTAPAMAM (G...

The ability of the guanine-rich strand of the human mitochondrial DNA (mtDNA) to form G-quadruplex structures (G4s) has been recently highlighted, suggesting potential functions in mtDNA replication initiation and mtDNA stability. G4 structures in mtDNA raise the question of their recognition by factors associated with the mitochondrial nucleoid. The mitochondrial transcription factor A (TFAM),...