https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2890%2980916-7

Solid-phase peptide synthesis: a practical approach : by E. Atherton and R.C. Sheppard; Oxford University Press; Oxford, 1989; ix + 203 pages; £27.00

This study aimed to prepare and optimize goserelin acetate (GOS) loaded hydrogel poly(d,l-lactic acid-co-glycolic acid) (PLGA) microsphere that is suitable for long-acting clinical treatment, investigate its structure, and regulate the initial release manner. Here, the PLGA microsphere containing Poloxamer hydrogel loaded with ∼15% (w/w) GOS was prepared by double-emulsion-solvent evaporation method and evaluated in terms of microscopic structure, physicochemical properties, and release manner in vitro and in vivo. Raman volume imaging and scanning electron microscopy studies revealed a core-shell Di-Depot structure of the microsphere, in which multi-GOS-loaded hydrogel depots were distributed in the core region. Under the interaction of hydrogel and PLGA depots, high encapsulation efficiency (94.16%) and low burst release (less than 2%) were achieved, along with the accompanying prolonged administration interval (49 days); an enhanced relative bioavailability 9.36-fold higher than that of Zoladex implant was also observed. Also, by addition of 1-5% acetic acid, the lag time was shortened to 6 days. The strategy for regulating the initial release provides new insights for manipulating the release behavior of the PLGA microspheres. The desirable property of the Poloxamer hydrogel PLGA microsphere indicated its promising application in controlled release drug delivery system.

Goserelin Acetate Loaded Poloxamer Hydrogel in PLGA Microspheres: Core-Shell Di-Depot Intramuscular Sustained Release Delivery System.

Drug repositioning has become a prevailing tactic as this strategy is efficient, economical and low risk for drug discovery. Meanwhile, recent studies have confirmed that small-molecule drugs can modulate the expression of disease-related miRNAs, which indicates that miRNAs are promising therapeutic targets for complex diseases. In this study, we put forward and verified the hypothesis that drugs with similar miRNA profiles may share similar therapeutic properties. Furthermore, a comprehensive drug-drug interaction network was constructed based on curated drug-miRNA associations. Through random network comparison, topological structure analysis and network module extraction, we found that the closely linked drugs in the network tend to treat the same diseases. Additionally, the curated drug-disease relationships (from the CTD) and random walk with restarts algorithm were utilized on the drug-drug interaction network to identify the potential drugs for a given disease. Both internal validation (leave-one-out cross-validation) and external validation (independent drug-disease data set from the ChEMBL) demonstrated the effectiveness of the proposed approach. Finally, by integrating drug-miRNA and miRNA-disease information, we also explain the modes of action of drugs in the view of miRNA regulation. In summary, our work could determine novel and credible drug indications and offer novel insights and valuable perspectives for drug repositioning.

In silico drug repositioning based on drug-miRNA associations.

Metal complexes with an N-terminally free and N-terminally acetylated polyhistidine region of Echis ocellatus venom, with an interesting His-rich motif present in numerous metal binding proteins from all kingdoms of life (DHDHDHHHHHHPGSSV-NH2 and Ac-DHDHDHHHHHHPGSSV-NH2) show the role of the free amino group in the thermodynamic enhancement of Cu2+, Ni2+ and Zn2+ binding. In the studied sequences, Cu2+ can be coordinated by different sets of imidazole rings, and a 3–10 helix is detected in close proximity of Cu2+ binding sites. The complexes are more stable than those with a typical His6-tag, despite a similar copper(II) coordination mode in both cases.

Uncapping the N-terminus of a ubiquitous His-tag peptide enhances its Cu2+ binding affinity

Gonadotropin-releasing hormone-Cu complex (Cu-GnRH) transcriptional activity in vivo in the female rat anterior pituitary gland.

A nickel(II) coordination polymer of succinic acid (1,4-butanedioic acid, H2succ), [Ni(succ)(H2O)4]n (1), was prepared and characterized in depth using IR and Raman spectroscopic methods and theore...

IR and Raman spectroscopic analysis, DFT modeling, and magnetic properties of a nickel(II) complex, [Ni(succ)(H2O)4]n

HENRYK - An endless source of metal coordination surprises.

Impact of the Cu(II) ions on the chemical and biological properties of goserelin - coordination pattern, DNA degradation, oxidative reactivity and in vitro cytotoxicity.

Colorectal cancer (CRC) is the third most commonly diagnosed form of cancer worldwide. Recent studies have indicated a strong correlation between microbial imbalance and the development of CRC. An abundance of Fusobacterium nucleatum, an anaerobic Gram-negative bacterium, has been considered a biomarker of CRC progression. Several investigations have also proposed that binding copper ions to various bacterial proteins enhances the CuII + e- ⇄ CuI redox cycle, which consequently promotes uncontrolled production of reactive oxygen species (ROS) and propels colorectal carcinogenesis. In this work, a multidisciplinary approach was applied to study the molecular relation of copper with the peptide models of FomA, a protein expressed by Fusobacterium nucleatum. The main goal was to investigate all the factors that tune the CuII + e- ⇄ CuI equilibrium. A linear peptide Fom1 (Ac-KGHGNGEEGTPTVHNE-NH2) and cyclic peptide Fom2 (cyclo-(KGHGNGEEGTPTVHNE)) were used as ligands. The coordination of CuI was deduced from the NMR data. The conditional dissociation constants KcondD defined the stability of CuI complexes. The electrochemical activity of CuII and CuI compounds was analysed using cyclic voltammetry. A quasi-reversible redox conversion CuII-peptide + e- ⇄ CuI-peptide was revealed for all studied systems. In the presence of ascorbic acid (HAsc), CuII complexes were immediately reduced to CuI species; however, their re-oxidation was kinetically sluggish. The HAsc-induced redox cycle provoked the metal-catalyzed oxidation (MCO) effect. That in the end prevented coordination of the re-appearing CuII ion to its initial binding site. The toxicity of the FomA-CuII/CuI complexes and their role in CRC progression were briefly discussed.

Paulina K. Walencik

Papers

IR and Raman spectroscopic analysis, DFT modeling, and magnetic properties of a nickel(II) complex, [Ni(succ)(H2O)4]n

HENRYK - An endless source of metal coordination surprises.

Impact of the Cu(II) ions on the chemical and biological properties of goserelin - coordination pattern, DNA degradation, oxidative reactivity and in vitro cytotoxicity.

The redox-active Cu-FomA complex: the mode that provides coordination of CuII/CuI ions during the reduction/oxidation cycle.

The Bioinspired Cuii/Cui-Peptide Systems with a Bis-His Coordination Environment – Rules and Limitations in the Design of Copper-Based Redox Mediators