Self assembly and hydrogelation of N-terminal modified tetrapeptide for sustained release and synergistic action of antibacterial drugs against methicillin resistant S. aureus.

Self assembly is a ubiquitous process of complex bio-molecules to perform various biological functions. This bottom-up approach applies in engineering of various nanostructures in different technological and biomedical applications. Here we report design and synthesis of phenolic acid conjugated tetra peptides which self assembled in uniform nanofibrils upon dissolution in aqueous solutions at physiological pH and formed stiff and transparent hydrogel. Gel inversion assay, HR-TEM, FT-IR, CD spectroscopy and rheometric analysis characterized the developed hydrogel (HG-2). This gel exhibits characteristics of thixotropy and injectability. Structure-gelation relationship studies of peptide revealed the importance of π-π interactions in self assembly and hydrogelation. Further, this hydrogel used for entrapment and sustained release of antibiotics, rifampicin and ciprofloxacin at physiological pH and temperature for 5 days. The hydrogelator peptide has shown moderate antibacterial activity alone, whereas in combination with rifampicin and ciprofloxacin showed a remarkable synergistic antibacterial activity against clinically relevant multidrug resistant methicillin resistant S. aureus (MRSA). Interestingly, this hydrogel neither cause significant damage to hRBCsnor to human keratinocyte up to hydrogelation concentrations tested by haemolytic and MTT assay. These characteristics of present peptide hold future promising soft materials for treatment of infections and drug delivery applications.

Significant destabilization of human telomeric G-quadruplex upon peptide binding: dramatic effect of flanking bases.

Human telomere is composed of highly repeated hexanucleotide sequence TTAGGG and a 3' single-stranded DNA tail. Many telomere G4 topologies characterized at atomic level by X-ray crystallography and NMR studies. Until now, various small ligands developed to interact with G-quadruplex mainly to stabilize the structure and least is known for its destabilization. In this study, we provide the first evidence of human telomeric G4 destabilization upon peptide binding in dilute and cell-mimicking molecular crowing conditions due to the changes in flanking bases of human telomeric sequences. Hence, our findings will open the new ways to target diseases related with increasing the efficiency of DNA replication, transcription or duplex reannealing.Communicated by Ramaswamy H. Sarma.