Structure-based computational design of antibody mimetics: challenges and perspectives.

The design of antibody mimetics holds great promise for revolutionizing therapeutic interventions by offering alternatives to conventional antibody therapies. Structure-based computational approaches have emerged as indispensable tools in the rational design of those molecules, enabling the precise manipulation of their structural and functional properties. This review covers the main classes of designed antigen-binding motifs, as well as alternative strategies to develop tailored ones.

C-based Multivalent Glycoporphyrins Inhibit SARS-CoV-2 Specific Interaction with the DC-SIGN Transmembrane Receptor.

Since WHO has declared the COVID-19 outbreak a global pandemic, nearly seven million deaths have been reported. This efficient spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is facilitated by the ability of the spike glycoprotein to bind multiple cell membrane receptors. Although ACE2 is identified as the main receptor for SARS-CoV-2, other receptors could play a role in viral entry.

Association strength of E6 to E6AP/p53 complex correlates with HPV-mediated oncogenesis risk.

Human papillomavirus (HPV) is recognized as the causative agent of cervical cancer in women, and it is associated with other anogenital and head/neck cancers. More than 120 types of HPV have been identified and many classified as high- or low-risk according to their oncogenic potential. One of its proteins, E6, has evolved to overcome the oncosuppressor functions of p53 by targeting this protein for degradation via interaction with the human ubiquitin-ligase E6AP.

Virus-inspired designs of antimicrobial nanocapsules.

Antimicrobial resistance is becoming a serious burden for drug design. The challenges are in finding novel approaches for effectively targeting a number of different bacterial strains, and in delivering these to the site of action. We propose here a novel approach that exploits the assembly of antimicrobial peptidic units in nanocapsules that can penetrate and rupture the bacterial membrane.

Nanocapsule designs for antimicrobial resistance.

The pressing need of new antimicrobial products is growing stronger, particularly because of widespread antimicrobial resistance, endangering our ability to treat common infections. The recent coronavirus pandemic has dramatically highlighted the necessity of effective antibacterial and antiviral protection. This work explores at the molecular level the mechanism of action of antibacterial nanocapsules assembled in virus-like particles, their stability and their interaction with mammal and antimicrobial model membranes.

Amino acid polymorphisms in the fibronectin-binding repeats of fibronectin-binding protein A affect bond strength and fibronectin conformation.

The cell surface contains cell wall-anchored proteins such as fibronectin-binding protein A (FnBPA) that bind to host ligands ( fibronectin; Fn) present in the extracellular matrix of tissue or coatings on cardiac implants. Recent clinical studies have found a correlation between cardiovascular infections caused by and nonsynonymous SNPs in FnBPA. Atomic force microscopy (AFM), surface plasmon resonance (SPR), and molecular simulations were used to investigate interactions between Fn and each of eight 20-mer peptide variants containing amino acids Ala, Asn, Gln, His, Ile, and Lys at positions equivalent to 782 and/or 786 in Fn-binding repeat-9 of FnBPA.

Structure-based design, synthesis and antitumoral evaluation of enulosides.

Enulosides, carbohydrate derivatives containing an α,β-unsaturated carbonyl unit, were designed and obtained in high yields and isomeric purity. All synthesized compounds exhibited antitumoral activity in micromolar range against four tested tumor cells lines, being the best results observed for HL-60 cells. These compounds open new possibilities to prepare an array of more active, site-specific or selective antitumor agents.

Efficient Biexciton Interaction in Perovskite Quantum Dots Under Weak and Strong Confinement.

Cesium lead halide perovskite quantum dots (PQDs) have emerged as a promising new platform for lighting applications. However, to date, light emitting diodes (LED) based on these materials exhibit limited efficiencies. One hypothesized limiting factor is fast nonradiative multiexciton Auger recombination.

QM/MM simulations of amyloid-β 42 degradation by IDE in the presence and absence of ATP.

The ability of the insulin-degrading enzyme (IDE) to degrade amyloid-β 42 (Aβ42), a process regulated by ATP, has been studied as an alternative path in the development of drugs against Alzheimer's disease. In this study, we calculated the potential of mean force for the degradation of Aβ42 by IDE in the presence and absence of ATP by umbrella sampling with hybrid quantum mechanics and molecular mechanics (QM/MM) calculations, using the SCC-DFTB QM Hamiltonian and Amber ff99SB force field. Results indicate that the reaction occurs in two steps: The first step is characterized by the formation of the intermediate.

Molecular dynamics simulations reveal a novel mechanism for ATP inhibition of insulin degrading enzyme.

Regulation of brain levels of the Amyloid-β 42 (Aβ42) polypeptide by IDE has recently been linked with possible routes for new therapies against Alzheimer's disease (AD). One important aspect is the regulatory mechanism of IDE by ATP, which is an IDE activator in degrading small peptides and an inhibitor in degrading larger peptides, such as Aβ42. This relationship was investigated in this study.

Synthesis and evaluation of (-)-Massoialactone and analogues as potential anticancer and anti-inflammatory agents.

(-)-Massoialactone, an α,β-unsaturated δ-lactone isolated from Cryptocarya massoia, and five analogues were synthesized and their antiproliferative and anti-inflammatory activities were evaluated. The lactones were able to mimic the "core" functional group required for the biological activity of their parent natural compounds suggesting that substantially altered analogues may retain their properties.