Article
Chemistry, Multidisciplinary
Jan Pawlas, Jon H. Rasmussen
Summary: This study demonstrates the feasibility of using Fmoc/t-Bu solid-phase peptide synthesis under aqueous conditions, utilizing a resin and solvent combination to improve resin swelling and solubility of starting materials. By developing a waste recycling method, the reuse of waste was achieved, reducing the amount of starting materials used and replacing hazardous solvents with an aqueous medium.
Article
Biochemistry & Molecular Biology
Aleksandra Walewska, Paulina Kosikowska-Adamus, Marta Tomczykowska, Bartosz Jaroszewski, Adam Prahl, Grzegorz Bulaj
Summary: Human beta-defensin 3 (HBD-3) is an antimicrobial and immunomodulatory peptide with multiple biological functions. This study optimized the synthetic method of HBD-3, improving the synthesis efficiency and enabling structural and functional studies. Additionally, an alternative synthesis method with improved oxidative folding was proposed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Peter H. G. Egelund, Sandip Jadhav, Vincent Martin, Henrik Johansson Castro, Franziska Richner, Sebastian Thordal Le Quement, Frank Dettner, Carolin Lechner, Ralph Schoenleber, Daniel Sejer Pedersen
Summary: This study explores the use of pyrrolidine as a base to expand the available solvent polarity space for green solid-phase peptide synthesis, investigating the effects of different solvent mixtures on Fmoc removal and coupling reactions, and comparing the synthesis results of different peptide targets.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2021)
Article
Chemistry, Multidisciplinary
Tatiana N. Tikhonova, Nataliya N. Rovnyagina, Zohar A. Arnon, Boris P. Yakimov, Yuri M. Efremov, Dana Cohen-Gerassi, Michal Halperin-Sternfeld, Nastasia V. Kosheleva, Vladimir P. Drachev, Andrey A. Svistunov, Peter S. Timashev, Lihi Adler-Abramovich, Evgeny A. Shirshin
Summary: This study revealed that the presence of ThT significantly modifies the structural and mechanical properties of Fmoc-FF hydrogel, resulting in a tenfold increase in gelation time and enhanced rigidity. ThT not only slowed down the formation kinetics of Fmoc-FF hydrogel, but also greatly improved its mechanical properties, suggesting a novel approach for controlling peptide hydrogels' micro-and macroscale properties.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
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)
Article
Chemistry, Multidisciplinary
Dhanya Karipal Padinjare Veedu, Luke A. Connal, Lara R. Malins
Summary: In this study, an electrochemical method for peptide late-stage modification using amidic side-chains is developed. The method enables the modification of glutamine residues and the introduction of high-value functionalities through electroauxiliary-assisted oxidation. The applicability of the method to complex peptide systems is demonstrated, as well as its potential for peptide stapling and functionalization.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
K. P. Nandhini, Fernando Albericio, Beatriz G. de la Torre
Summary: Fmoc and Boc groups are commonly used protective groups in solid-phase peptide synthesis, and the Mmsb linker allows for their simultaneous use. Peptide-O-Mmsb-Resin remains stable during the removal of Fmoc and Boc using piperidine and trifluoroacetic acid (TFA) treatment. This strategy has advantages such as preventing diketopiperazine formation in sequences prone to this side reaction, enabling on-resin cyclization without the use of common organic reagents, and facilitating on-resin disulfide formation in unprotected peptides.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Adam Pribylka, Milan Pastorek, Martin Grepl, Eva Pribylka Schutznerova
Summary: By utilizing green bases, solvents, and solvent mixtures, the Fmoc solid-phase peptide synthesis procedures were optimized and the impact on side products was evaluated. The new green protocols demonstrated good applicability in practical synthesis, effectively reducing the generation of harmful by-products.
Article
Chemistry, Organic
Yihui Xie, Danni Luo, Jesse Wiener, Sicheng Tang, Sergiy Chepyshev, Christian Schafmeister
Summary: This study reports the Fmoc protection of functionalized bis-amino acid building blocks using a temporary Cu2+ complexation strategy, along with an efficient multikilogram-scale synthesis of bis-amino acid precursors. Solid-phase Fmoc/tBu chemistry enables the synthesis of stereochemically and functionally diverse spiroligomers, promoting the development of applications. Four tetramers were assembled and their secondary structures were determined using two-dimensional nuclear magnetic resonance spectroscopy.
Article
Chemistry, Multidisciplinary
Peisi Liao, Hongmei Liu, Chunmao He
Summary: In this study, we developed a reliable method for the synthesis of human SelF and described the synthetic route in detail. The synthesis involved a desulfurization process and removal of protective groups, resulting in the production of a large quantity of homogenous SelF. The reduction potential and oxidoreductase activity of SelF were determined, supporting its proposed function.
Article
Chemistry, Organic
Yuqi Zhang, Junlang Chen, Chunmao He
Summary: In this study, a novel bifunctional reagent was developed for late-stage protection of peptide cysteine, enabling facile N-terminal and side-chain caging for model peptides and proteins. Additionally, a one-pot ligation and photolysis strategy was successfully applied in the synthesis of the mini-protein chlorotoxin. Furthermore, the utility of the reagent as a bifunctional linker for traceless solid-phase chemical ligation was extended.
Article
Multidisciplinary Sciences
Richard C. Brewster, Irati Colmenero Labeaga, Catriona E. Soden, Amanda G. Jarvis
Summary: The study demonstrates the synthesis of cyclic peptides through solid-phase synthesis of peptides containing metal-binding amino acids, combined with peptide macrocyclization using peptide cyclase 1 (PCY1), and shows the resulting cyclic peptides as competent catalysts for metal ligands. The research reveals that PCY1 can tolerate peptides containing amino acids with classic inorganic and organometallic ligands as side chains, paving the way for efficient development of cyclic peptides as metal ligands.
ROYAL SOCIETY OPEN SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Hynek Macha, Marek Korinek, Ladislav Droz, Karel Nesmerak
Summary: The simple RP-HPLC method using an internal standard accurately determines resin loading in solid-phase peptide synthesis, suitable for common synthesis types with reliable results for monitoring in multi-step synthesis.
MONATSHEFTE FUR CHEMIE
(2021)
Article
Chemistry, Physical
Stanislav A. Petrov, Aleksei E. Machulkin, Rostislav A. Petrov, Alexander N. Tavtorkin, Galina N. Bondarenko, Sergey A. Legkov, Ilya E. Nifant'ev, Valentina D. Dolzhikova, Nikolay V. Zyk, Alexander G. Majouga, Elena K. Beloglazkina
Summary: A new low molecular mass organic gelator based on specific compounds was synthesized and examined for its ability to gelate various organic solvents. The microstructure of the gels was studied using SEM, showing different morphologies for different solvents. Analysis of FTIR, H-1 NMR and UV-vis data revealed that the gelator molecules aggregate through N-H/O hydrogen bonding, hydrophobic interaction, and pi-pi-staking.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Biochemistry & Molecular Biology
Michael J. Bird, Philip E. Dawson
Summary: This study presents a practical method for the synthesis of C-terminal hydrazide peptides. By utilizing specific resin linkers, peptides containing 40 amino acids were successfully synthesized, demonstrating the broad applicability of this method.
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
Chemistry, Multidisciplinary
Sisa Chalan-Gualan, Ivan Ramos-Tomillero, Thibault Terencio, Lola De Lima, Daniela G. Navas-Leon, Margarita Suarez, Nelson Santiago Vispo, Fernando Albericio, Hortensia Rodriguez
Summary: Cysteine-based perfluoroaromatic compounds, such as hexafluorobenzene (HFB) and decafluorobiphenyl (DFBP), were synthesized and used as versatile cores to construct molecular systems with interesting properties. DFBP was found to be more effective than HFB for the monoalkylation of thiols. Antibody-perfluorinated conjugates were prepared using thiol through two different strategies, demonstrating that bioconjugation did not affect the macromolecular entity. Spectroscopic characterization and theoretical calculations were used to evaluate the molecular properties of the synthesized compounds. Molecular docking predicted that cysteine-based DFBP derivatives could be potential binders for topoisomerase II alpha and COX-2, suggesting their potential as anticancer agents and candidates for anti-inflammatory treatment.
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
Biochemistry & Molecular Biology
Umair Rauf, Ghulam Shabir, Saba Bukhari, Fernando Albericio, Aamer Saeed
Summary: This paper summarizes the recent advancements in the synthesis and applications of ferrocene derivatives reported from 2016 to date. It focuses on the synthesis of diverse classes of organic compounds with ferrocene scaffolds and the development of applications of ferrocene-based organometallic compounds, particularly in the fields of biology, medicine, bio-sensing, chemosensing, asymmetric catalysis, materials, and industry.
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
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.
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.
