Article
Biochemistry & Molecular Biology
Henry Madubuike, Natalie Ferry
Summary: The demand for high-performance biocatalysts has been driven by the need for cleaner alternatives to current chemical syntheses. However, biocatalysts often exhibit low performance in industrial conditions. In this study, an engineered acetyl xylan esterase (BaAXE) was modified to improve its performance in a hydrophilic organic solvent. Rational design approach was used to introduce charged residues in the solvent-affecting region of the enzyme, resulting in mutants with improved activity and stability. Computational analysis revealed the role of novel intermolecular interactions in enhancing the performance of the mutants. This work supports the importance of protein engineering in optimizing the characteristics of wild-type enzymes.
Article
Biochemistry & Molecular Biology
Iredia D. D. Iyamu, Yingzhao Zhao, Prakash T. T. Parvatkar, Bracken F. F. Roberts, Debora R. R. Casandra, Lukasz Wojtas, Dennis E. E. Kyle, Debopam Chakrabarti, Roman Manetsch
Summary: A compound with promising antimalarial activity against chloroquine-resistant and chloroquine-sensitive strains of the parasite was identified through screening and structure-activity relationship studies. The essential features necessary for its activity and properties were determined through extensive research.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Silvano Paternoster, Peter Simpson, Elena Kokh, Husun Sheyma Kizilkaya, Mette Marie Rosenkilde, Ricardo L. Mancera, Damien J. Keating, Massimiliano Massi, Marco Falasca
Summary: Metabolic diseases like obesity and type 2 diabetes have led to the development of novel GLP-1 mimetics for treatment, although they may come with side effects. A potent GLP-1 secretion agent derived from food lipids, oleoyl-LPI, shows promising pharmacological activity.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Neurosciences
Maria Lazarova, Daniela S. Tsekova, Lyubka P. Tancheva, Kiril T. Kirilov, Diamara N. Uzunova, Lyubomir T. Vezenkov, Elina R. Tsvetanova, Albena Alexandrova, Almira P. Georgieva, Petja T. Gavrilova, Stela T. Dragomanova, Maria G. Papazova, Yordan S. Handzhiyski, Reni E. Kalfin
Summary: The study revealed that four newly synthesized galantamine derivatives have lower toxicity, do not impair memory performance in healthy mice, demonstrate potential for inhibition of AChE and antioxidant activity.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Chemistry, Multidisciplinary
Xingguang Cai, Sacha Javor, Bee Ha Gan, Thilo Kohler, Jean-Louis Reymond
Summary: The pH-activity profiling shows that antimicrobial peptide dendrimers (AMPDs) are effective in killing Klebsiella pneumoniae and Methicillin-resistant Staphylococcus aureus (MRSA) at pH = 8.0 but not at pH = 7.4, likely due to stronger electrostatic binding to bacterial cells at higher pH. This phenomenon could also apply to polymyxin B and other polycationic antimicrobials.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Kazuya Kobayashi, Takuya Otani, Saki Ijiri, Yuki Kawasaki, Hiroki Matsubara, Takahiro Miyagi, Taishi Kitajima, Risa Iseki, Katsuyasu Ishizawa, Naoka Shindo, Kouta Okawa, Kouta Ueda, Syun Ando, Momoka Kawakita, Yasunao Hattori, Kenichi Akaji
Summary: The introduction of an aromatic substituent into a HEA-type BACE1 inhibitor enhanced inhibitory activity, with the R-configuration improving activity and methyl substitution decreasing activity. Isosteres with different hydroxyl and methyl configurations were prepared using a branched synthesis approach, and the effect on inhibitory activity was evaluated. Derivatives with various substituents at the P1' site showed clear effects on BACE1 activity, leading to the identification of a highly potent inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Food Science & Technology
Weijia Li, Haoming Li, Jia Li, Jia Xu, Li Fang, Chunlei Liu, Dan Wu, Weihong Min
Summary: This study explored the relationship between the digestion of walnut peptide (<3 kDa) and its antioxidant activity, focusing on the inhibitory effect of DPP-IV on the antioxidant peptide KGHLFPN. The results showed that after simulated gastrointestinal digestion, the antioxidant capacity of the peptides was enhanced, while their tertiary structures became weaker and secondary structures became random coiled. The study also found that the antioxidant walnut peptide KGHLFPN exhibited good DPP-IV inhibitory activity, and the optimal time for oral absorption of KGHLFPN in vivo was found to be 4-8 hours. Therefore, walnut protein hydrolysate (<3 kDa) can be used as an antioxidant precursor, and walnut peptides have the potential to serve as food-derived antioxidants.
LWT-FOOD SCIENCE AND TECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rina Nakamura, Toshifumi Akizawa, Motomi Konishi
Summary: We discovered a hydrolytic peptide called JAL-TA9 and modeled its catalytic center using computational simulations. We found that GSGYR and RYGSG peptides may form catalytic triads and oxyanion holes. These peptides can cleave A beta 11-29 and suppress its aggregation, showing similar cleavage positions. This study highlights the importance of Catalytides in understanding structure-activity relationships.
Article
Biochemical Research Methods
Wouter van Bergen, Johannes F. Hevler, Wei Wu, Marc P. Baggelaar, Albert J. R. Heck
Summary: Most drugs target proteins, and determining the exact drug binding sites on proteins is crucial for understanding their effects. A strategy called PhosID-ABPP was developed to identify drug binding sites using immobilized metal-affinity chromatography and phosphonate affinity tags. This method successfully identified over 500 unique binding sites of the drug PF-06672131. PhosID-ABPP also revealed differences in binding sites between intact cells and cell lysates, and captured a previously elusive binding site on the epidermal growth factor receptor.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Chemistry, Medicinal
Bengisu Turgutalp, Merve Uslu, Sinem Helvacioglu, Mohammad Charehsaz, Enise Ece Gurdal, Wolfgang Sippl, Fatih Kocabas, Mine Yarim
Summary: The pivotal role of MEIS1 in cardiac regeneration and HSC regulation was highlighted, and a potent MEIS inhibitor, MEISi-1, inducing HSC expansion was identified. Lead optimization on MEISi-1 led to the synthesis of 45 novel analogues, with 11 compounds identified as potent inhibitors, including 4h, 4f, and 4b exhibiting the best inhibitory profile on MEIS1 target genes. Predicted pharmacokinetics properties of the compounds matched drug-likeness criteria, without cytotoxicity or mutagenicity observed.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Food Science & Technology
Shuyu Zhang, Liu Dong, Zhijie Bao, Songyi Lin
Summary: In this study, a novel peptide VNAVL was synthesized by removing the C-terminal histidine, and the effects of removing histidine on antioxidant activity, immunomodulatory activity, and secondary structure were discussed. The results showed that VNAVL exhibited lower antioxidant activity and no immunomodulatory activity compared to VNAVLH.
Article
Chemistry, Medicinal
Mariko Saitoh, Kentaro Takayama, Yoshimi Roppongi, Takahiro Shimada, Akihiro Taguchi, Atsuhiko Taniguchi, Yoshio Hayashi
Summary: This study focused on the hydrophobic residues of DF-3 and designed a more potent peptide DF-100, which showed twice the inhibitory ability as DF-3 by replacing a methionine residue with homophenylalanine. This report provides a new platform for a 14-mer peptide muscle enhancer.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Physical
Yuchen Zhang, Yichen Yu, Ruipu Wang, Yi Dai, Lixia Bao, Minghao Li, Yaoyuan Zhang, Qi Liu, Dong Xiong, Qin Wu, Daxin Shi, Kangcheng Chen, Yuming Li, Guiyuan Jiang, Evgenii Kondratenko, Hansheng Li
Summary: ZrO2-based catalysts have been widely studied in propane dehydrogenation (PDH) due to their cost-effectiveness, eco-friendliness, and excellent catalytic performance. This research focuses on the structure-activity relationship and mechanistic analysis of Ga2O3/ZrO2 in PDH, where GaOx acts as either an active site or a promoter. The results reveal that the rate of propene formation is influenced by the Ga2O3 loading, which affects the evolution of Ga2O3 species and the formation of new active sites. The DFT calculations also indicate that Ga2O3/ZrO2 exhibits enhanced activation ability and lower reaction barriers compared to bare ZrO2.
JOURNAL OF CATALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Hongmok Kwon, Hyunsoo Ha, Hayoung Jeon, Jaebong Jang, Sang-Hyun Son, Kiho Lee, Song-Kyu Park, Youngjoo Byun
Summary: Hepsin, a type II transmembrane serine protease, is overexpressed in several types of cancer including prostate cancer. Compound 22a, a p-guanidinophenylalanine-based dipeptide analog, shows strong hepsin-inhibitory activity and selectivity over matriptase, suggesting it could be a potential prototype for structural optimization of hepsin inhibitors.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Muhammad Danish, Muhammad Asam Raza, Hurria Rani, Arusa Akhtar, Muhammad Nadeem Arshad, Abdullah M. Asiri
Summary: This study successfully synthesized four new phenylalanine-based sulfonamides and characterized and optimized them using FTIR spectroscopy, Density Functional Theory, and Single Crystal X-Ray Diffraction technique. Compound 1 exhibited high activity in antioxidant and enzyme inhibition, being the most active among all synthetic molecules.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Multidisciplinary Sciences
Philippe Schwaller, Benjamin Hoover, Jean-Louis Reymond, Hendrik Strobelt, Teodoro Laino
Summary: The article discusses the research results on Transformer Neural Networks learning atom-mapping information, proposing a new method for reaction mapping that shows remarkable performance in terms of accuracy and speed, providing a new solution for chemical reaction tasks.
Article
Chemistry, Medicinal
Elena Zakharova, Markus Orsi, Alice Capecchi, Jean-Louis Reymond
Summary: This study successfully discovered new non-hemolytic anticancer peptides using recurrent neural networks and machine learning methods, demonstrating the first application of machine learning in this field.
Article
Chemistry, Multidisciplinary
Johannes Morstein, Alice Capecchi, Konstantin Hinnah, ByungUk Park, Jerome Petit-Jacques, Reid C. Van Lehn, Jean-Louis Reymond, Dirk Trauner
Summary: Most bioactive molecules need to cross or be distributed into biological membranes, and natural products often have lipid modifications to facilitate molecule-membrane interactions. Lipidated natural products primarily contain saturated medium-chain lipids, and lipid conjugation can significantly modulate the permeability, cellular retention, subcellular localization, and bioactivity of small molecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Valentina Rossetti, Jean-Louis Reymond
Summary: In this article, we share the aims, development, challenges, and outcome of the National Center of Competence in Research (NCCR) TransCure's temporary learning and artistic path called 'Vitaport - Was unser Korper transpor-tiert' in Bern. This project involved NCCR TransCure researchers and students from the Bern School of Design, who developed ceramic objects, texts, and information graphics to take the public on a multidisciplinary journey through the human body.
Article
Chemistry, Multidisciplinary
Tin Manh Ho, Stephan Berger, Philipp Mueller, Celine Simonin, Jean-Louis Reymond, Christoph von Ballmoos, Daniel G. Fuster
Summary: The goal of this research was to investigate the physiological and molecular function of NHA2, develop a high resolution kinetic transport assay, and identify specific compounds targeting NHA2. The interdisciplinary and interfaculty effort led to successful results and provided important information for further research and drug development.
Article
Chemistry, Multidisciplinary
Jean-Louis Reymond
Summary: Quantifying molecular similarity is crucial in drug discovery and optimization. This review focuses on computational methods developed in the NCCR TransCure interdisciplinary network for studying physiology, structural biology, and pharmacology of ion channels and membrane transporters. The review highlights the use of molecular similarity measures in scaffold hopping, predicting off-target effects, and creating chemical space maps.
Article
Chemistry, Medicinal
Ye Buehler, Jean-Louis Reymond
Summary: The generated databases (GDBs) list billions of possible molecules through systematic enumeration following simple rules of chemical stability and synthetic feasibility. The originality of GDB molecules can be assessed by comparing their Bemis and Murcko molecular frameworks (MFs) with those in public databases. This comparison revealed that GDB-13s MFs had diverse ring sizes and ring systems without linker bonds, making them attractive targets for synthetic chemistry aiming at innovative molecules.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Joel S. Bloch, Alan John, Runyu Mao, Somnath Mukherjee, Jeremy Boilevin, Rossitza N. Irobalieva, Tamis Darbre, Nichollas E. Scott, Jean-Louis Reymond, Anthony A. Kossiakoff, Ethan D. Goddard-Borger, Kaspar P. Locher
Summary: C-linked glycosylation is essential for the trafficking, folding, and function of secretory and transmembrane proteins involved in cellular communication processes. Cryogenic-electron microscopy structures of Caenorhabditis elegans CMT reveal how the CMT recognizes the glycosylation sequon and triggers conformational activation of the donor substrate, enabling C-glycosylation of proteins. These findings have implications for understanding human diseases and potential therapeutic targeting of specific CMT paralogs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Hippolyte Personne, Thissa N. Siriwardena, Sacha Javor, Jean-Louis Reymond
Summary: Here, we demonstrate that dipropylamine (DPA) can effectively reduce aspartimide formation in high-temperature solid-phase peptide synthesis (SPPS) compared to piperidine (PPR). DPA is easily accessible, inexpensive, non-toxic, and odorless, making it a promising alternative to PPR. Furthermore, DPA yields good results in SPPS of non-aspartimide-prone peptides and peptide dendrimers.
Article
Chemistry, Multidisciplinary
Etienne Bonvin, Jean-Louis Reymond
Summary: We redesigned the branches of PAMAM dendrimers to improve their stability by modifying the amide carbonyl group. The resulting i-PAMAM dendrimers have the same carbon framework as PAMAMs but differ in the position of the carbonyl group. Compared to PAMAMs, which are difficult to purify, we synthesized i-PAMAMs using solid-phase peptide synthesis and purified them using preparative reverse phase HPLC. Our i-PAMAM dendrimers showed no degradation over time and exhibited potent antimicrobial activities against both Gram-negative and Gram-positive bacteria.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Matheus A. Meirelles, Jean-Louis Reymond
Summary: This study presents an optimized synthesis method for a probe used in studying protein N-glycosylation in eukaryotic cells. The yields and reaction times of three phosphate coupling steps were improved by adjusting reagents and conditions. An efficient purification protocol was also developed to obtain the pure product.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Medicinal
Ye Buehler, Jean-Louis Reymond
Summary: Identifying novel ring fragments (RFs) and acyclic fragments (AFs) from public databases and natural products can provide potential opportunities for drug innovation in fragment-based drug discovery.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Etienne Bonvin, Hippolyte Personne, Thierry Paschoud, Jeremie Reusser, Bee-Ha Gan, Alexandre Luscher, Thilo Kohler, Christian van Delden, Jean-Louis Reymond
Summary: By introducing peptoid units into antimicrobial peptides, the antimicrobial effects can be retained with reduced toxicity to human cells, and under specific conditions, there may be a transition towards intracellular targeting.
ACS INFECTIOUS DISEASES
(2023)
Article
Chemistry, Multidisciplinary
David Kreutter, Jean-Louis Reymond
Summary: This study introduces a new tool for computer-aided synthesis planning that can automatically learn organic reactivity and perform retrosynthesis. The tool combines a triple transformer loop and a multistep tree search algorithm to propose short synthetic routes based on commercial starting materials.
Article
Biochemistry & Molecular Biology
Stephane Baeriswyl, Hippolyte Personne, Ivan Di Bonaventura, Thilo Koehler, Christian van Delden, Achim Stocker, Sacha Javor, Jean-Louis Reymond
Summary: The peptide alpha-helix structure can be right-handed or left-handed depending on the chirality of amino acids, and mixed chirality peptides require special conditions to form alpha-helices; the study of mixed chirality alpha-helices in short peptides composed of natural residues reveals that they can overlap with homochiral alpha-helices and exhibit resistance to proteolysis.
RSC CHEMICAL BIOLOGY
(2021)
