Our aim is to investigate the phase segregation and the structure of multi-component bio-inspired phospholipid vesicles via dissipative particle dynamics. The chemical distinction in the phospholipid species arises due to different head and tail group moieties, and molecular stiffness of the hydrocarbon tails. The individual amphiphilic phospholipid molecular species are represented by a hydrophilic head group and two hydrophobic tails. The distinct chemical nature of the moieties is modeled effectively via soft repulsive interaction parameters, and the molecular rigidity is tuned via suitable three-body potential constants. We demonstrate the formation of a stable hybrid vesicle through the self-assembly of the amphiphilic phospholipid molecules in the presence of a hydrophilic solvent. We investigate and characterize the phase segregation and the structure of the binary vesicles for different phospholipid mixtures. Our results demonstrate macroscopic phase separation for phospholipid mixtures composed of species with different hydrocarbon tail groups. We also investigate the relationship between the phase segregation and thermodynamic variables such as interfacial line tension and surface tension, and obtain correspondence between existing theory and experiments, and our simulation results. We report variations in the molecular chain stiffness to have negligible contributions to the phase segregation in the mixed bilayer, and to demonstrate shape transformations of the hybrid vesicle. Our results can be used to design novel bio-inspired hybrid vehicles for potential applications in biomedicine, sensing, imaging and sustainability.

Xeno nucleic acids (XNAs) are artificial genetic systems based on sugar-modified nucleotides. Herein, we investigate double-headed nucleotides as a new XNA. A new monomer, AT, is presented, and together with...

The enzymatic conversion of isothiazolo[4,3‐d]pyrimidine‐based adenosine (tzA) and 2‐aminoadenosine (tz2‐AA) analogues to the corresponding isothiazolo[4,3‐d]pyrimidine‐based inosine (tzI) and guanosine (tzG) derivatives is evaluated and compared to the conversion of native adenosine to inosine. Henri–Michaelis–Menten analyses provides the foundation for a high‐throughput screening assay, and the efficacy of the assay is showcased by fluorescence‐based analysis of tzA conversion to tzI in the presence of known and newly synthesized inhibitors.

A new fluorescent ribonucleoside alphabet (mthN) consisting of pyrimidine and purine analogues, all derived from methylthieno[3,4‐d]pyrimidine as the heterocyclic core, is described. Large bathochromic shifts and high microenvironmental susceptibility of their emission relative to previous alphabets derived from thieno[3,4‐d]pyrimidine (thN) and isothiazole[4,3‐d]pyrimidine (tzN) scaffolds are observed. Subjecting the purine analogues to adenosine deaminase, guanine deaminase and T7 RNA polymerase indicate that, while varying, all but one enzyme tolerate the corresponding mthN/mthNTP substrates. The robust emission quantum yields, high photophysical responsiveness and enzymatic accommodation suggest that the mthN alphabet is a biophysically viable tool and can be used to probe the tolerance of nucleoside/tide‐processing enzymes to structural perturbations of their substrates.

Ribosome‐inactivating proteins, a family of highly cytotoxic proteins, interfere with protein synthesis by depurinating a specific adenosine residue within the conserved α‐sarcin/ricin loop of eukaryotic ribosomal RNA. Besides being biological warfare agents, certain RIPs have been promoted as potential therapeutic tools. Monitoring their deglycosylation activity and their inhibition in real time have remained, however, elusive. Herein, we describe the enzymatic preparation and utility of consensus RIP hairpin substrates in which specific G residues, next to the depurination site, are surgically replaced with tzG and thG, fluorescent G analogs. By strategically modifying key positions with responsive fluorescent surrogate nucleotides, RIP‐mediated depurination can be monitored in real time by steady‐state fluorescence spectroscopy. Subtle differences observed in preferential depurination sites provide insight into the RNA folding as well as RIPs’ substrate recognition features.