ANTHONY MARTIN
Researcher – CNRS, HDR
Anthony R. Martin received his PhD from the University of Montpellier in 2011 under the supervision of Prof. Michael Smietana and Dr. Jean-Jacques Vasseur, working on the synthesis and self-assembly of borono(oligo)nucleotides. He then joined Prof. Steven Nolan’s group (Saint-Andrews University) as a postdoctoral researcher to work on late transition metal coordination and their applications in homogeneous catalysis. In 2013, he moved to the Institute of Chemistry of Nice in Dr. Benhida’s group where he was appointed Chargé de Recherche — CNRS in 2014. There, he mainly focused his research on medicinal chemistry programs devoted to the tackling of chemoresistance in cancers. Additionally, he developed chemical biology tools to monitor and probe enzymatic activities in live cells. In 2020, Anthony moved to the Institut des Biomolécules Max Mousseron (Montpellier), in Dr Amblard’s group, where his current researches encompass various aspects of peptide chemistry and the exploration of new modalities for the targeted degradation of proteins.
Contact:
anthony.martin@umontpellier.fr
Covalent‑reversible peptide‑based protease inhibitors. Design, synthesis, and clinical success stories.
Amino Acids 2023, https://link.springer.com/article/10.1007/s00726-023-03286-1
Feral, A. R. Martin, A. Desfoux, M. Amblard et L. Vezenkov.
Abstract
Dysregulated human peptidases are implicated in a large variety of diseases such as cancer, hypertension, and neurodegeneration. Viral proteases for their part are crucial for the pathogens’ maturation and assembly. Several decades of research were devoted to exploring these precious therapeutic targets, often addressing them with synthetic substrate-based inhibitors to elucidate their biological roles and develop medications. The rational design of peptide-based inhibitors offered a rapid pathway to obtain a variety of research tools and drug candidates. Non-covalent modifiers were historically the first choice for protease inhibition due to their reversible enzyme binding mode and thus presumably safer profile. However, in recent years, covalent-irreversible inhibitors are having a resurgence with dramatic increase of their related publications, preclinical and clinical trials, and FDA-approved drugs. Depending on the context, covalent modifiers could provide more effective and selective drug candidates, hence requiring lower doses, thereby limiting off-target effects. Additionally, such molecules seem more suitable to tackle the crucial issue of cancer and viral drug resistances. At the frontier of reversible and irreversible based inhibitors, a new drug class, the covalent-reversible peptide-based inhibitors, has emerged with the FDA approval of Bortezomib in 2003, shortly followed by 4 other listings to date. The highlight in the field is the breathtakingly fast development of the first oral COVID-19 medication, Nirmatrelvir. Covalent-reversible inhibitors can hipothetically provide the safety of the reversible modifiers combined with the high potency and specificity of their irreversible counterparts. Herein, we will present the main groups of covalent-reversible peptide-based inhibitors, focusing on their design, synthesis, and successful drug development programs.
Synthesis, photophysics, and theoretical calculations of styryl-based fluorophores harboring substituted benzothiazole acceptors
Photochem. Photobiol. A, 2023, 435, 114287, https://doi.org/10.1016/j.jphotochem.2022.114287
M. Safir Filho, E. Santos Moraes, L. Camargo da Luz, F. da Silveira Santos, A. R. Martin, R. Benhida. L. G. Teixeira Alves Duarte, F. S. Rodembusch
Abstract
This study describes the synthesis, photophysical characterization, and TD-DFT calculation of a series of benzothiazole-based styryl fluorophores (F1–F5) harboring a D-π-A structure. The compounds were obtained through a simple and efficient synthetic route using low-cost starting materials. The investigation and analysis of their photophysical properties enable the assessment of the effect of four substituted benzothiazole moieties (A) and two types of π-conjugated frameworks (phenyl vs thienyl) in solution and in solid state. The fluorophores disclose absorption in the ultraviolet-blue region with a moderate solvatochromic effect and a single emission band located at the blue-green spectral range. In the solid state, the fluorophores showed emission in the green-orange regions with a relatively large Stokes shift. The systematic UV–vis solvatochromism study and theoretical predictions using the CPCM model reveals the increment in the dipole moment of the systems in an excited state with the solvent dielectric constant. These compounds showed high fluorescence quantum yield in solution and in solid-state and could be further exploited for solid-state lighting devices, or embedded in the design of biological dyes.
The Unexpected Helical Supramolecular Assembly of a Simple Achiral Acetamide Tecton Generates Selective Water Channels
Abstract
Achiral 2-hydroxy-N-(diphenylmethyl)acetamide (HNDPA) crystallizes in the P61 chiral space group as a hydrate, building up permeable chiral crystalline helical water channels. The crystallization-driven chiral self-resolution process is highly robust, with the same air-stable crystalline form readily obtained under a variety of conditions. Interestingly, the HNDPA supramolecular helix inner pore is filled by a helical water wire. The whole edifice is mainly stabilized by robust hydrogen bonds involving the HNDPA amide bonds and CH… π interactions between the HNDPA phenyl groups. The crystalline structure shows breathing behavior, with completely reversible release and re-uptake of water inside the chiral channel under ambient conditions. Importantly, the HNDPA channel is able to transport water very efficiently and selectively under biomimetic conditions. With a permeability per channel of 3.3 million water molecules per second in large unilamellar vesicles (LUV) and total selectivity against NaCl, the HNDPA channel is a very promising functional nanomaterial for future applications.