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1.
Nat Commun ; 14(1): 1381, 2023 Mar 13.
Article in English | MEDLINE | ID: mdl-36914623

ABSTRACT

Lack of reproducibility hampers molecular devices integration into large-scale circuits. Thus, incorporating operando characterization can facilitate the understanding of multiple features producing disparities in different devices. In this work, we report the realization of hybrid molecular graphene field effect transistors (m-GFETs) based on 11-(Ferrocenyl)undecanethiol (FcC11SH) micro self-assembled monolayers (µSAMs) and high-quality graphene (Gr) in a back-gated configuration. On the one hand, Gr enables redox electron transfer, avoids molecular degradation and permits operando spectroscopy. On the other hand, molecular electrode decoration shifts the Gr Dirac point (VDP) to neutrality and generates a photocurrent in the Gr electron conduction regime. Benefitting from this heterogeneous response, the m-GFETs can implement optoelectronic AND/OR logic functions. Our approach represents a step forward in the field of molecular scale electronics with implications in sensing and computing based on sustainable chemicals.

2.
J Mol Biol ; 433(19): 167177, 2021 09 17.
Article in English | MEDLINE | ID: mdl-34329642

ABSTRACT

Neutralizing antibodies (nAbs) hold promise as therapeutics against COVID-19. Here, we describe protein engineering and modular design principles that have led to the development of synthetic bivalent and tetravalent nAbs against SARS-CoV-2. The best nAb targets the host receptor binding site of the viral S-protein and tetravalent versions block entry with a potency exceeding bivalent nAbs by an order of magnitude. Structural studies show that both the bivalent and tetravalent nAbs can make multivalent interactions with a single S-protein trimer, consistent with the avidity and potency of these molecules. Significantly, we show that the tetravalent nAbs show increased tolerance to potential virus escape mutants and an emerging variant of concern. Bivalent and tetravalent nAbs can be produced at large-scale and are as stable and specific as approved antibody drugs. Our results provide a general framework for enhancing antiviral therapies against COVID-19 and related viral threats, and our strategy can be applied to virtually any antibody drug.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19 Drug Treatment , COVID-19/immunology , Mutation , SARS-CoV-2/immunology , Angiotensin-Converting Enzyme 2 , Animals , Antibodies, Neutralizing/chemistry , Antibodies, Neutralizing/genetics , Antibodies, Viral/chemistry , Antibodies, Viral/genetics , Antiviral Agents/therapeutic use , Binding Sites , Chlorocebus aethiops , HEK293 Cells , Humans , Immunoglobulin G , Models, Molecular , Protein Binding , Protein Engineering , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
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