iBB

In a recent study led by Pedro Gois´s team (Faculdade Farmácia da Universidade de Lisboa), with collaboration from researchers Hovione FarmaCiencia SA and iBB (Sandra Pinto), a novel multivalent platform of NHS-activated acrylates was developed for the site-selective chemical appendage of multiple functionalities on native peptides. The results were published in Chem Commun and were included in the 2022 issue of Pioneering Investigators.

The effectiveness of antiplasmodial drugs against the blood stage of infection is increasingly threatened by the emergence and spread of drug-resistant parasites. Here a small library of “half-sandwich” cyclopentadienylruthenium(II) compounds of the general formula [(η5-C5R5)Ru(PPh3)(N-N)][PF6] was screened for activity against the blood stage of CQ-sensitive 3D7-GFP, CQ-resistant Dd2, and artemisinin-resistant IPC5202 Plasmodium falciparum strains and the liver stage of Plasmodium berghei. We showed that some of the compounds are potent dual-stage antiplasmodials, displaying Plasmodium falciparum-selective accumulation in infected erythrocytes. The study was coordinated by researchers from Faculdade de Farmácia with collaboration of researchers from IHMT, IMM and iBB-IST (Sandra Pinto). The results were published in Inorg. Chem. 

Graphene quantum dots (GQDs) possess excellent optical properties, high photostability, aqueous solubility and bio-compatibility. In this work, we report for the first time a two-step methodology for the efficient covalent functionalization of GQDs with corrole macrocycles. The resulting hybrids were explored as imaging agents and thus their internalization and distribution in live animal cells was evaluated in cancer cell lines (MCF-7, human breast adenocarcinoma cell line) using confocal laser scanning microscopy. The study was coordinated by researchers from CQE-IST (Ermelinda Maçoas) and University of Aveiro (Carla Santos) and also with collaboration of researchers from Complutense University of Madrid and iBB-IST (Sandra Pinto). The results were published in Carbon.

The ability of Saccharomyces cerevisiae to overcome the stress induced by cytotoxic compounds depends on the activity of plasma membrane transporters of the ABC superfamily, presumably through the questionable unspecific efflux of multiple drugs and xenobiotic compounds. A recent paper by iBB researchers provides new insights into the biological role of the ABC transporter of the pleiotropic drug resistance family of putative drug efflux pumps Pdr18, proposed to mediate ergosterol incorporation in plasma membrane. Pdr18 expression was found to help cells to counteract acetic acid-induced decrease of plasma membrane lipid order, increase the non-specific membrane permeability and decrease the transmembrane electrochemical potential. Results support the notion that Pdr18-mediated multistress resistance is linked to the status of plasma membrane lipid environment related with ergosterol content and the associated plasma membrane properties. The paper, published in Scientific Reports, results from the PhD project of Cláudia Godinho, advised by Prof. Isabel Sá-Correia from BSRG-iBB in collaboration with Fábio Fernandes and Sandra Pinto from BSIRG-iBB).

A new strategy to modify cellulose with the short antimicrobial hexapeptide MP196 (RWRWRW-NH2) is proposed by BERG and BSIRG researchers that uses fusions of Cys-terminated derivatives of MP196 and a carbohydrate binding module (CBM). CBM3-MP196-modified cellulose hydrogels displayed antibacterial activity that was significantly higher when compared with controls. This versatile concept offers a toolbox for the functionalization of different cellulose materials with a broad choice in peptides. the paper was published in Acta Biomaterialia. The work was funded by project CBM-X.

The role of the bcaC  trimeric autotransporter adhesion (TAA) gene in the virulence of Burkholderia cenocepacia has been disclosed by iBB researchers Andreia Pimenta, Dalila Mil-Homens, Sandra Pinto and Arsénio Fialho in a report published in Microbes and Infection. TAAs are homotrimeric proteins of the outer membrane of many Gram-negative pathogens that play a key role in adhesion to host cells. Two insertional-mutants for TAA bcaC and histidine kinase (HK) BCAM0218 genes were constructed. Findings indicate that bcaC encodes for a large multifunctional TAA that has hemagglutination activity and is also required for maximal host cell adherence. The neighbor BCAM0218 HK encoding gene was identified as a critical player that negatively controls the expression of the bcaC TAA gene. All together, the findings represent a step forward for a better characterization of the subset of B. cenocepacia TAA-encoding genes. This article was selected as the highlighted article of the July 2020 issue of the Microbes and Infection journal.

Zinc surfaces coated with nanostructured ZnO flowers has received increasing attention as a versatile biomaterial for medical applications. A collaborative work between researchers from CQE (Marta Alves, Catarina Santos and Fátima Montemor) and iBB (Dalila Mil-Homens, Sandra Pinto) describes the successful functionalization of these surfaces with cooper (Cu), iron (Fe) or manganese (Mn) oxides (Ox). The in vitro study of  these surfaces,  by fibroblast viability,  hemocompatibility, and  chick  chorioallantoic membrane (CAM) assays revealed the potential brought by CuOx functionalization for anti-cancer applications, with the antagonist behaviour of the surfaces functionalized with MnOx, and in a less extent with FeOx, favouring wound healing in traumatic  processes. Despite the possible correlation between biocompatibility and   hydroxyapatite   precipitation,   no   correlation   could   be   drawn with the corrosion activity, study by immersion and electrochemical techniques, of these surfaces. The study resulted from. The results were published in Colloids and Surfaces B: Biointerfaces.