Oligoarginine peptide structure and its effect on cell penetration in ocular drug delivery.

Oligoarginine cell-penetrating peptides (CPPs) are short peptides that can enhance drug delivery into cells and are of particular interest in ocular topical formulations for age-related macular degeneration (AMD) treatments. The length and structural characteristics of these peptides are considered crucial for drug delivery. This study investigates how oligoarginine length (R) affects their penetration mechanism, drug delivery capabilities, and antimicrobial properties, providing insights into their potential roles in AMD treatment delivery.

Developing Novel Biointerfaces: Using Chlorhexidine Surface Attachment as a Method for Creating Anti-Fungal Surfaces.

There is an increasing focus in healthcare environments on combatting antimicrobial resistant infections. While bacterial infections are well reported, infections caused by fungi receive less attention, yet have a broad impact on society and can be deadly. Fungi are eukaryotes with considerable shared biology with humans, therefore limited technologies exist to combat fungal infections and hospital infrastructure is rarely designed for reducing microbial load.

Location-Dependent Lanthanide Selectivity Engineered into Structurally Characterized Designed Coiled Coils.

Herein we report unprecedented location-dependent, size-selective binding to designed lanthanide (Ln ) sites within miniature protein coiled coil scaffolds. Not only do these engineered sites display unusual Ln selectivity for moderately large Ln ions (Nd to Tb), for the first time we demonstrate that selectivity can be location-dependent and can be programmed into the sequence. A 1 nm linear translation of the binding site towards the N-terminus can convert a selective site into a highly promiscuous one.

Stability of Cell-Penetrating Peptide anti-VEGF Formulations for the Treatment of Age-Related Macular Degeneration.

Aim: The development of a polyarginine cell-penetrating peptide (CPP) could enable the treatment of age-related macular degeneration, with drugs like bevacizumab, to be administered using eye drops instead of intravitreal injections. Topical formulations have a vast potential impact on healthcare by increasing patient compliance while reducing the financial burden. However, as the ocular preparations may contain several doses, it is essential to understand the stability of the bevacizumab+CPP conjugate produced.

Tuning coordination chemistry through the second sphere in designed metallocoiled coils.

The metal hydration state within a designed coiled coil can be progressively tuned across the full integer range (3 → 0 aqua ligands), by careful choice of a second sphere terminal residue, including the lesser used Trp. Potential implications include a four-fold change in MRI relaxivity when applied to lanthanide coiled coils.

Location dependent coordination chemistry and MRI relaxivity, in designed lanthanide coiled coils.

Herein, we establish for the first time the design principles for lanthanide coordination within coiled coils, and the important consequences of binding site translation. By interrogating design requirements and by systematically translating binding site residues, one can influence coiled coil stability and more importantly, the lanthanide coordination chemistry. A 10 Å binding site translation along a coiled coil, transforms a coordinatively saturated Tb(Asp)(Asn) site into one in which three exogenous water molecules are coordinated, and in which the Asn layer is no longer essential for binding, Tb(Asp)(HO).

De Novo Design of Xeno-Metallo Coiled Coils.

Bioinorganic chemists aspire to achieve the same exquisite and highly controlled inorganic chemistry featured in biology. An exciting mimetic approach involves the use of miniature artificial protein scaffolds designed de novo (often based on the coiled coil (CC) scaffold), for reproducing native metal ion sites and their function. Recently, there is increased interest, instead, in the design of xeno-metal sites within CC assemblies.