Article
Chemistry, Organic
Flavie Bouchet, Heiner Atze, Michel Arthur, Melanie Etheve-Quelquejeu, Laura Iannazzo
Summary: The study utilized the traceless Staudinger ligation to functionalize the C2 position of second generation beta-lactamase inhibitors based on a diazabicyclooctane (DBO) scaffold. Biological evaluation demonstrated that the route provided access to a DBO that showed superior inhibition against two out of the five beta-lactamases tested compared to commercial relebactam.
Article
Multidisciplinary Sciences
Nathalie Ollivier, Magalie Senechal, Remi Desmet, Benoit Snella, Vangelis Agouridas, Oleg Melnyk
Summary: Phosphorylation is a mechanism used by cells to promote protein-biomolecule association. In this study, the authors demonstrate the effects of interactions between proteins equipped with positively charged arginines and peptides harboring negatively charged phosphoserines, enabling rate acceleration and chemical processes under dilute conditions.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Ivan Sanchez-Campillo, Judit Miguel-Gracia, Periklis Karamanis, Juan B. Blanco-Canosa
Summary: Chemical protein synthesis is a consolidated field that utilizes the high chemospecificity of amide-forming reactions, particularly the native chemical ligation (NCL), alongside new technologies such as the Ser/Thr ligation and the alpha-ketoacid-hydroxylamine (KAHA) condensation. The NCL was initially designed for the ligation of peptides with a C-terminal thioester and an N-terminal cysteine. This study combines the Nbz and Bt approaches in a versatile linker, 1,2-diaminobenzene (Dbz), demonstrating high yields of ligation and the potential for transseleoesterification reactions. The results indicate faster NCL kinetics with Bt precursors, enabling rapid transthioesterification.
Article
Biochemistry & Molecular Biology
Florent Kerdraon, Gemma Bogard, Benoit Snella, Herve Drobecq, Muriel Pichavant, Vangelis Agouridas, Oleg Melnyk
Summary: Thiol-based catalysts are commonly used for chemical protein synthesis, but the development of selenol-based catalysts is still in its early stages. This study compared different selenols for their ability to promote thiol-thioester exchanges and demonstrated the successful total synthesis of a biologically active human chemotactic protein using a selected selenol compound.
Article
Physics, Multidisciplinary
Can B. Uzundal, Sasawat Jamnuch, Emma Berger, Clarisse Woodahl, Paul Manset, Yasuyuki Hirata, Toshihide Sumi, Angelique Amado, Hisazumi Akai, Yuya Kubota, Shigeki Owada, Kensuke Tono, Makina Yabashi, John W. Freeland, Craig P. Schwartz, Walter S. Drisdell, Iwao Matsuda, Tod A. Pascal, Alfred Zong, Michael Zuerch
Summary: Second harmonic generation (SHG) spectroscopy is commonly used to investigate surface chemistry, interfacial chemistry, and symmetry properties in solids, but the complexity of novel materials makes interpretation of experiments difficult. Polarization-resolved extreme ultraviolet (XUV-SHG) spectroscopy demonstrates element-specific angular anisotropy investigations for the first time, paving the way for future angle and time-resolved XUV-SHG studies with elemental specificity in condensed matter systems.
PHYSICAL REVIEW LETTERS
(2021)
Review
Pharmacology & Pharmacy
Olive Finding, Johan Sellner
Summary: Options for disease-modifying therapies in multiple sclerosis have expanded in the past two decades, with second-generation drugs offering higher efficacy and fewer side effects.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
Bongki Cho, Seung-Jun Yoo, So Yeon Kim, Chang-Hun Lee, Yun-Il Lee, Seong-Ryong Lee, Cheil Moon
Summary: In this study, divergently modified peptide analogs derived from EPO showed potent neuroprotective effects against oxidative stress without inducing cell proliferation. One of the peptides, ML1-h3, exhibited unique binding potency to EPOR and inhibited neuronal death and brain injury under hypoxic stress.
Article
Chemistry, Multidisciplinary
Jordan P. Hempfling, Emily R. Sekera, Amar Sarkar, Amanda B. Hummon, Dehua Pei
Summary: Efficient and convenient method for producing recombinant proteins with free N-terminal cysteines has been reported. Site-specific labeling of the resulting proteins at the N-terminus was achieved through a novel genetic fusion and sequential enzymatic processing.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Kota Nomura, Yuta Maki, Ryo Okamoto, Ayano Satoh, Yasuhiro Kajihara
Summary: Research has shown that key reactions based on amino thioacids can form glycopeptides, providing a new method for synthesizing homogeneous glycoproteins. This new approach can generate glycoproteins within a few steps from peptides and glycosyl asparagine thioacid.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Riley J. Giesler, Paul Spaltenstein, Michael T. Jacobsen, Weiliang Xu, Mercedes Maqueda, Michael S. Kay
Summary: Native chemical ligation (NCL) allows for total chemical synthesis of proteins, but poor peptide segment solubility is a common challenge. A traceless linker, Fmoc-Glu(AlHx)-OH, temporarily attached to Glu side chains, overcomes this issue. Demonstrated efficient incorporation, stability, and rapid removal characteristics make it a promising tool for challenging synthetic peptides and proteins preparation.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Alyson M. Curry, Elizabeth Barton, Wenjia Kang, Daniel V. Mongeluzi, Yana Cen
Summary: This study developed simple activity-based chemical probes for investigating active sirtuin content and successfully enabled cell imaging of sirtuin activity change, providing new tools for future drug discovery strategies.
Article
Engineering, Electrical & Electronic
Ismail A. Buliyaminu, Md Abdul Aziz, Syed Shaheen Shah, Zain Hassan Yamani
Summary: This study successfully enhanced the electrocatalytic properties of zinc oxide towards water oxidation by decorating its surface with palladium nanoparticles. By optimizing the preparation of PdNPs-AZO electrodes, the electrodes exhibited optimum behavior towards water oxidation.
JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
(2022)
Article
Chemistry, Organic
Xiao-Lei Xie, Jing-Ze Qi, Xiao-Cui Wan, Suo-De Zhang, Yan-Ni Zhang, Ge-Min Fang
Summary: We present a robust and practical method for chemical protein synthesis using an o-nitrobenzyl group as a temporary protective group. Through further investigation, we establish a reliable strategy for the quantitative photodeprotection of the o-nitrobenzyl group. This stable protective group is successfully applied in the chemical synthesis of a programmed death ligand 1 fragment, providing a practical approach for hydrazide-based native chemical ligation.
Article
Materials Science, Ceramics
Hye-Rim Jeong, Tae-Hwan Huh, Byung Hyo Kim, Young-Je Kwark
Summary: In this study, a conductive Si/C/N/Ni nanocomposite was successfully prepared and characterized. The results showed that the distribution of nickel nanoparticles was uniform throughout the nanocomposite due to the use of a nitrogen-rich polysilazane precursor as the matrix. Additionally, nickelocene acted as a catalyst, promoting the growth of nickel silicide crystalline phase and turbostratic carbon phase at low temperatures. Moreover, the dehydrogenation reaction facilitated by nickelocene improved the crystallinity of turbostratic carbon, resulting in enhanced electrical conductivity of the nanocomposite.
CERAMICS INTERNATIONAL
(2022)
Article
Chemistry, Multidisciplinary
Michael S. Crocker, Zihang Deng, Jeffrey N. Johnston
Summary: Amide synthesis is widely used in drug development and peptide synthesis, but waste elimination in this process has had limited success. Umpolung amide synthesis has been developed as a method for enantioselective synthesis, but it cannot forge N-aryl amides. This study presents a direct synthesis method for N-aryl amides using a simple Bronsted base as a promoter, using alpha-fluoronitroalkanes and N-aryl hydroxyl amines.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Biochemistry & Molecular Biology
Beatriz G. G. de la Torre, Fernando Albericio
Summary: While the world was battling with the COVID-19 Omicron wave at the end of 2021, except for China, most countries ended 2022 with COVID-19 being treated like the flu. As a result, the U.S. Food and Drug Administration (FDA) only authorized 37 new drugs this year, compared to an average of 52 in the previous four years. This marks the second lowest number of drug approvals in the last six years, even though it may change in the future. The decrease in FDA approvals mainly applies to small molecule drugs, while biologics and TIDES have remained relatively constant.
Review
Biochemistry & Molecular Biology
Fatima Tuz Zahra, Aamer Saeed, Khansa Mumtaz, Fernando Albericio
Summary: The tropylium ion is a versatile non-benzenoid aromatic species that serves as a catalyst in numerous organic transformations. It outperforms transition-metal catalysts with its yield, moderate conditions, non-toxic byproducts, functional group tolerance, selectivity, and ease of handling. This review highlights the importance of the tropylium ion as an environmentally safe catalyst and summarizes its role in various organic reactions.
Article
Infectious Diseases
Maria Veronica Humpola, Roque Spinelli, Melina Erben, Virginia Perdomo, Georgina Guadalupe Tonarelli, Fernando Albericio, Alvaro Sebastian Siano
Summary: In this study, analogs of two antimicrobial peptides, C10:0-A2 and TA4, were designed and synthesized, and non-proteinogenic amino acids were used to improve their therapeutic properties. The physicochemical properties and antimicrobial activity of these analogs were analyzed. The results showed that substitution with D- and N-methyl amino acids could enhance stability against enzymatic degradation and modulate the therapeutic properties of antimicrobial peptides and lipopeptides. The study provides insights into the design and optimization of antimicrobial peptides for improved stability and therapeutic efficacy. TA4(dK), C10:0-A2(6-NMeLys), and C10:0-A2(9-NMeLys) were identified as the most promising molecules for further studies.
Article
Chemistry, Multidisciplinary
K. P. Nandhini, Mahama Alhassan, Clinton G. L. Veale, Fernando Albericio, Beatriz G. de la Torre
Summary: The solid-phase synthesis of Met-containing peptides often leads to the formation of impurities, Met(O) and sulfonium salt, due to oxidation and S-alkylation reactions. These reactions occur during the final acidolytic cleavage step. In this study, two new cleavage solutions were developed to eliminate oxidation and reduce S-alkylation. The optimal mixture for Cys-containing peptides was TFA-anisole-TMSCl-Me2S-TIS with triphenyl phosphine, while TIS was not required for other peptides. Both cleavage solutions were effective for sensitive amino acids like Cys and Trp. The sulfonium salt was successfully reversed to free Met-containing peptide by heating with acetic acid.
Review
Biochemistry & Molecular Biology
Alexander C. Martins, Fernando Albericio, Beatriz G. de la Torre
Summary: The year 2022 saw the successful control of the COVID-19 pandemic in most countries through social and hygiene measures and vaccination campaigns. However, there was a decrease in total drug approvals by the FDA, particularly for small molecules. The Biologics class, on the other hand, maintained its figures with the authorization of 15 novel molecules.
Article
Chemistry, Medicinal
Othman Al Musaimi, Danah Al Shaer, Fernando Albericio, Beatriz G. de la Torre
Summary: In 2022, a total of 37 new drug entities were approved, with TIDES class drugs gaining five authorizations, consisting of four peptides and one oligonucleotide. The majority of these drugs (23 out of 37) were first-in-class and received fast-track designation by the FDA. This analysis focuses on the TIDES approved in 2022, examining their chemical structure, medical target, mode of action, administration route, and common adverse effects.
Article
Biotechnology & Applied Microbiology
Fanny Guzman, Monica Arostica, Tanya Roman, Dina Beltran, Adriana Gauna, Fernando Albericio, Constanza Cardenas
Summary: Solid-Phase Peptide Synthesis (SPPS) is a widely used technique in research and production. Three different laboratory protocols have been implemented to fulfill diverse requirements. The results show that each protocol yields different purification and can be chosen based on specific needs.
ELECTRONIC JOURNAL OF BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sinenhlanhla N. Mthembu, Amit Chakraborty, Ralph Schonleber, Fernando Albericio, Beatriz G. de la Torre
Summary: Morpholine, scoring 7.5 in greenness and not being regulated, is a promising candidate for Fmoc removal in solid-phase peptide synthesis (SPPS). Morpholine in dimethylformamide (DMF) (50%-60%) effectively removes Fmoc in SPPS, reduces diketopiperazine formation, and nearly eliminates aspartimide formation. Somatostatin has been successfully synthesized using 50% morpholine in DMF with the same purity as when using 20% piperidine-DMF, serving as proof of concept.
JOURNAL OF PEPTIDE SCIENCE
(2023)
Review
Chemistry, Multidisciplinary
Jessica T. Mhlongo, Ayman Y. Waddad, Fernando Albericio, Beatriz G. de la Torre
Summary: Antimicrobial peptides (AMPs) are promising candidates for combating multidrug resistance due to their heterogenous structures and broad-spectrum action. The combined use of AMPs with other antimicrobial agents provides a new arsenal of drugs with synergistic action, inhibiting the development of drug resistance. This review discusses various synergies of AMPs with antimicrobials and miscellaneous agents, providing guidance for improved clinical outcomes.
Review
Chemistry, Medicinal
Ghulam Shabir, Aamer Saeed, Wajeeha Zahid, Fatima Naseer, Zainab Riaz, Nafeesa Khalil, Mary J. Muneeba, Fernando Albericio
Summary: Fluorine substitution has been extensively explored for improving drug properties, such as increasing biological activity and enhancing stability. Selective substitution of fluorine onto therapeutic or diagnostic drugs can enhance pharmacokinetic and physicochemical properties. The use of fluorine in radiolabeling and PET imaging has also been studied. This review reports on FDA-approved fluorinated drugs and provides examples from various therapeutic and diagnostic drugs.
Article
Biochemical Research Methods
Tanya Roman, Gerardo Acosta, Beatriz G. de la Torre, Constanza Cardenas, Fanny Guzman, Fernando Albericio
Summary: This study presents an optimized procedure for activating 2-chlorotrityl chloride (2-CTC) resin, reducing the use of activation reagent and activation time. It also demonstrates the feasibility of reusing the resin and achieving different degrees of activation by varying the amount of thionyl chloride (SOCl2).
METHODS AND PROTOCOLS
(2023)
Article
Biochemistry & Molecular Biology
Babita Kushwaha, Sinenhlanhla N. Mthembu, Anamika Sharma, Fernando Albericio, Beatriz G. de la Torre
Summary: We have synthesized disulfide-reducing agents DPDT and DMPDT from serinol and methyl serinol, respectively. DPDT demonstrated higher stability than DMPDT. The reducing capacity of DPDT was found to be comparable to that of DTT, and its effectiveness was evaluated in both liquid and solid phases.
Review
Chemistry, Multidisciplinary
K. P. Nandhini, Danah Al Shaer, Fernando Albericio, Beatriz G. G. de la Torre
Summary: Peptide Nucleic Acids (PNAs) are important mimics of DNA/RNA that can effectively bind with high affinity and specificity. Due to their metabolic stability, PNAs have broad applications in various fields. However, PNA synthesis faces challenges such as difficulties in preparing monomers and their solubility, as well as obstacles related to intra/inter chain aggregation and side reactions. Different protecting group strategies can be employed to overcome these hurdles and optimize the synthesis process.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Chemistry, Organic
K. P. Nandhini, Sikabwe Noki, Edikarlos Brasil, Fernando Albericio, Beatriz G. de la Torre
Summary: Peptide Nucleic Acids (PNAs) are a class of synthetic biomolecules with great potential in medicine. A new PNA SPS strategy based on a safety-catch protecting group scheme has been developed, allowing the synthesis of PNAs using Boc as a temporal protecting group.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Rafel Prohens, Rafael Barbas, Beatriz G. de la Torre, Fernando Albericio, Antonio Frontera
Summary: This article reports on the crystal structure and properties of Oxyma-B, an important racemization suppressor for peptide synthesis. Through a combination of experimental and computational methods, the solid-state landscape and hydration tendency of this substance have been revealed.