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Genomic DNA adopts B‐form canonically. Besides, the oligonucleotides can adopt various non‐canonical secondary structures. These are hairpins, cruciforms, triplexes, quadruplexes (G4), i‐motifs etc. G4s are usually formed by the guanine rich oligonucleotides and are found in both DNA and RNA. G4s are more frequently distributed in telomeres, promoter oncogenes, immunoglobulin switch regions, ribosomal DNA etc. Recently, it has been established that G4s are intriguingly connected with different human diseases including cancer. Stabilization of G4s by designed molecules or drugs impedes the transcription of several oncogenes and also creates encumbrance to the telomere biogenesis which is very important in impediment of cancer. G4 is treated as an important molecular target in the discovery of anti‐cancer drugs. Among the G4 targeting molecules, peptides draw sincere attention due to its small size, simple synthetic methodology, low cytotoxicity and cellular permeability. In this review, our main discussion revolves around the formation of G4, distribution of G4 in genome, structurally diverse peptides (linear, cyclic, branch, conjugated) having potential to target G4 structures and its future perspectives. [ABSTRACT FROM AUTHOR]

G‐quadruplex (G4) is one of the non‐canonical nucleic acid structures that regulate multiple key biological processes. The formation of G4 hinders the progression of cancer. The molecular entities which can stabilize the G4 structure are very important to design anticancer therapeutics. Herein, it is described that a synthetic dendron‐like peptide, Cδ3‐(YYEE)‐E co‐assembles with G4 DNA in aqueous buffer containing Na+ ions. Various orthogonal biophysical studies have established the co‐assembly phenomenon. In silico, molecular docking studies also corroborate the results obtained from biophysical experiments. Importantly, the co‐assembly enhances the thermal stability of G4 DNA compared to free G4 DNA. The peptide inhibits the activity of telomerase enzyme which is found to be over‐expressed in most of the cancer cells and also down‐regulates the c‐Myc oncogenic expression. The peptide exhibits significant cytotoxic effect on cancer cells (HeLa and U2OS) compared to non‐cancer cells (HEK293) under similar experimental conditions. The study highlights the applicability of a synthetic bioactive peptide as a putative anticancer therapeutic. [ABSTRACT FROM AUTHOR]

Protein misfolding and subsequent generation of amyloid fibrils are associated with a wide range of diseases e. g. Alzheimer's, Huntington's, Parkinson's, type II diabetes, cystic fibrosis, and many others. Aromatic amino acid residues of polypeptide/protein are supposed to play a critical role in formation and stabilization of amyloid fibrils. Herein, we report a synthetic peptide, ALYLV (peptide 1), corresponding to B14‐18 of insulin, that forms nanofibrillar aggregates upon self‐association in aqueous medium. Staining with congo red (CR) and thioflavin t (ThT) establish that these organized nano‐assemblies are amyloidogenic in nature. Interestingly, the structural modification of peptide 1 replacing the centrally located tyrosine residue with valine, ALVLV (peptide 2), significantly reduces the assembly propensity as well as the amyloidogenicity of peptide 2 compared to peptide 1. MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) cell survival assay reveals the cytotoxicity of the aggregated peptides on HeLa cells upon 48 h of exposure. Overall, the study explores the aggregation potential, amyloidogenicity, and cytotoxicity of a hotspot of insulin and pinpoints the role of aromatic amino acid residue in amyloidosis. This outcome also illuminates the peptide nano‐assemblies for various biotechnological applications. [ABSTRACT FROM AUTHOR]