Self-aggregation of reverse bis peptide conjugate derived from the unstructured region of the prion protein

A novel bis scaffold containing a pentapeptide PHGGG, derived from the prion octarepeat, forms fibrils of nanometric dimensions, thus indicating that certain segments in the unstructured region of the prion protein may facilitate an initial fibrillation event

Copper-metalated peptide palindrome derived from prion octarepeat: synthesis, aggregation, and oxidative transformations

We report construction of a bis-pentapeptide conjugate 4 containing truncated pentapeptide sequence from prion octarepeats. Its copper-laden derivative 5 demonstrated a propensity for aggregate formation, which was studied by atomic force microscopy. Oxidative biochemical transformations catalyzed by 5 were evaluated by nucleic acid cleavage and by neurotransmitter oxidation, in the presence of external co-oxidants. Preliminary mechanistic analysis provides a hint for the involvement of reactive oxygen species in such transformations

Kinetic evaluation of a metalated diglycine conjugate as a functional mimetic of phosphate ester hydrolase

The crucial role of phosphate ester hydrolysis in various biological processes has spurred vigorous research activities to understand mechanisms of phosphate ester hydrolysis and to develop model systems that assist the above-mentioned reaction in a catalytic fashion. In the present study, we describe a novel, metalated peptide conjugate 4 possessing phosphate ester hydrolyzing activity against a phosphate monoester, diester, and a RNA chemical model. The design of conjugate 4 is inspired by the ATCUN binding tripeptide motif of serum albumin and involves tethering of two diglycine units by a flexible 1,3-diaminopropane linker. Detailed kinetic investigations of phosphate ester hydrolysis using model substrates and efforts to decipher underlying mechanisms are presented

Reusable photonucleases: plasmid scission by a uranyl ion impregnated adenine homopolymer in the presence of visible light and sunlight

Relaxation of supercoiled plasmid by uranyl ions impregnated on a adenylated polymeric support has been observed in the presence of visible light and sunlight. This insoluble polymer support permits facile reusability of the catalytic system and it failed to cleave lysozyme under the conditions employed for plasmid modification

Plasmid relaxation induced by copper metalated diglycine conjugates under heterogeneous reaction conditions

This paper reports synthesis and plasmid modification activities of a new class of insoluble copper-metalated diglycine conjugates, containing aliphatic linkers of varying length. Besides providing significant rate enhancement for model phosphate ester cleavage, these constructs also displayed efficient supercoiled plasmid scission, in the absence of co-oxidants, under heterogeneous catalytic conditions. Heterogeneous catalysis of plasmid relaxation by copper metalated diglycine conjugates is reported

Enforcing aggregation in a dipeptide conjugate

A bis-dipeptide scaffold (PH)2 DAB, derived from the N-terminal octa-repeats of the cellular prion protein, displayed remarkable nanoscopic self-assembly in solution. The ultrastructural details of the peptide filaments so obtained were probed by transmission electron microscopy and optical microscopy. Synthesis of the bis-dipeptide conjugate, its metalation and micrographs confirming the formation of fibrillar networks are presented

Ruthenium-metallated adenine nucleobase polymers as novel reagents for catalytic cleavage of phosphate esters

A ruthenium-impregnated resin has been used for the catalytic cleavage of model phosphate ester (P-ester) substrates and highly efficient hydrolytic rate enhancements were obtained. Remarkably, million-fold rate acceleration was observed for a phosphodiester substrate. A thorough Michaelis-Menten kinetic analysis of this resin-catalyzed hydrolytic reaction, using three different phosphate monoester and diester substrates, is presented in this communication

Catalytic transformations with copper-metalated diglycine conjugates

A series of copper-metalated, water-soluble bis-diglycine conjugates were synthesized and characterized through spectroscopic methods. These conjugates were evaluated for the cleavage of phosphodiester substrates, supercoiled plasmid relaxation in the presence of co-oxidants, and for the oxidation of a diphenolic substrate, 2,6-dimethoxyphenol. Appreciable rate enhancements were observed for these reactions and the oxidative nucleolytic cleavage activity and phenol oxidative coupling was presumably manifested via formation of reactive oxygen species

A reusable zigzag copper(II) coordination polymer with bio-essential constituents as a facile DNA scission agent

A copper(II) coordination polymer has been synthesized in the form of an infinite zigzag chain where each metal is bonded to one glycine, two adenine, one nitrate anion and a water molecule giving a distorted octahedral coordination geometry with N3O3 donor set. Each chain is hydrogen-bonded through C-H···O and N-H···O interactions on both sides leading to an overall polymeric structure. This compound not only shows facile chemical nuclease activity for pBR322 supercoiled DNA but also can be reused keeping its scission activity unchanged

Kinetic and mechanistic investigations of phosphodiester cleavage catalyzed by uranyl ion impregnated adenylated homopolymer

Accelerated hydrolysis of model phosphodiester substrates assisted by a uranyl ion immobilized adenylated homopolymer is reported. This catalytic system is amenable to efficient recycling thereby considerably expanding the scope of actinide ion catalyzed phosphodiester hydrolysis