Article
Biochemistry & Molecular Biology
Bilge Bicak
Summary: The aim of this study is to investigate the molecular structure and interactions of the antihypertensive peptide Val-Trp using molecular mechanical, quantum mechanical, and spectroscopic methods. The peptide's structure was optimized and analyzed, and its interactions with ACE, AT1R, and Renin were studied through molecular docking and molecular dynamics simulation. The ADME analysis provided valuable information about the feasibility of Val-Trp as an antihypertensive drug.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
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
Chemistry, Multidisciplinary
Lucy R. Hart, Charlotta G. Lebedenko, Saige M. Mitchell, Rachel E. Daso, Ipsita A. Banerjee
Summary: In this study, in silico studies were conducted to design diterpene and polyphenol-peptide conjugates that can potentially target over-expressed breast tumor cell receptors. The mutated peptides were created by inducing point mutations into a known tumor-targeting peptide sequence. Molecular docking studies and molecular dynamics simulations were performed to study the binding interactions and stability of the peptide conjugates with the receptors. The results showed enhanced binding interactions and stable receptor-ligand complexes, suggesting the potential therapeutic applications of these conjugates.
APPLIED SCIENCES-BASEL
(2022)
Article
Environmental Sciences
Hongzhao Xiang, Qiaomei Sun, Wenjing Wang, Sai Li, Xi Xiang, Zhiqiang Li, Xiaoxiang Liao, Hui Li
Summary: This study investigated the interaction mechanism between AHTN and HSA, revealing that the binding between AHTN and HSA is a moderate strength spontaneous process driven by hydrophobic forces. AHTN acts as a competitive inhibitor to weaken the esterase-like activity of HSA, potentially impairing the function of HSA.
Article
Biochemistry & Molecular Biology
Manivel Perumal, Parthiban Marimuthu, Xiumin Chen
Summary: This study investigated the binding mechanisms between 5-CQA and OVA, revealing that the complex formation is driven by electrostatic and hydrogen-bonding interactions, and also affects the structure of OVA. Molecular docking results showed hydrogen bond interactions between 5-CQA and specific residues of OVA, with good agreement between experimental values and MD simulation results.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Food Science & Technology
Xiaobo Dong, Chao Wan, Aiyun Huang, Huaide Xu, Hongjie Lei
Summary: Umami peptides from Hypsizygus marmoreus hydrolysate were purified and identified. Their binding mechanism with T1R1/T1R3 receptor was investigated using computational simulations. Five novel umami peptides were obtained and their interaction forces with the receptor were analyzed. These findings contribute to the development of umami peptides in edible mushrooms.
Article
Biochemistry & Molecular Biology
Lisa Michelle Barber, Zakir Hussain, Merlin Thomas, Andrew Hung
Summary: Phosphorylation of GLO1 alters its structure and affects its activity and interaction with substrates, potentially leading to cellular damage.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Spectroscopy
Ruhul Quds, Md. Amiruddin Hashmi, Zarmin Iqbal, Riaz Mahmood
Summary: In this study, the interaction between Mancozeb and human hemoglobin was investigated using spectroscopic techniques, molecular docking, and molecular dynamic simulation. The results showed that Mancozeb tightly binds to Hb, induces conformational changes, and impairs its function.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2022)
Article
Biochemistry & Molecular Biology
Suvro Biswas, Shafi Mahmud, Mohasana Akter Mita, Shamima Afrose, Md. Robiul Hasan, Mst. Sharmin Sultana Shimu, Md. Abu Saleh, Gomaa Mostafa-Hedeab, Mohammed Alqarni, Ahmad J. Obaidullah, Gaber El-Saber Batiha
Summary: This study selected 23 antimicrobial peptides and predicted their structure using PEP-FOLD 3.5. The peptides were docked to the SARS-CoV-2 spike protein receptor-binding domain (RBD) to study their inhibitory capability. Four peptides with high binding free energy and docking scores were identified. Molecular dynamics (MD) simulations further verified the docking results. Allergenicity and toxicity predictions indicated that the identified peptides were non-allergenic and non-toxic.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Md Afjalus Siraj, Md. Sajjadur Rahman, Ghee T. Tan, Veronique Seidel
Summary: The molecular docking approach revealed that friedelin and alpha-amyrin had the strongest binding affinity towards CB1 and engaged in stable non-bonding interactions close to the active site. The triterpenes studied demonstrated good capacity to penetrate the blood-brain barrier, supporting the antinociceptive and sedative properties of Vernonia patula.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ruifang Li, Jiasha Wu, Fuyang He, Qingpeng Xu, Kedong Yin, Shang Li, Weitong Li, Ao Wei, Lan Zhang, Xin-Hui Zhang, Beibei Zhang
Summary: Researchers designed a set of CGA-N12 analogues that showed stronger antifungal activity compared to the original compound CGA-N12. These analogues were able to kill invasive Candida species and their persist cells, as well as inhibit biofilm formation and eradicate preformed biofilms.
BIOORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Gozde Yalcin-Ozkat, Ronak H. Ersan, Mahmut Ulger, Seda T. Ulger, Serdar Burmaoglu, Ilkay Yildiz, Oztekin Algul
Summary: The increase in drug-resistant strains of Mycobacterium tuberculosis has driven researchers to seek new drug targets. In this study, the antitubercular activity of benzimidazole derivatives was experimentally determined, and molecular docking studies revealed their interaction with the DprE1 enzyme.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Fatima Doganc, Ismail Celik, Gokcen Eren, Marcel Kaiser, Reto Brun, Hakan Goker
Summary: A series of monocationic new guanidinobenzimidazole derivatives were synthesized and evaluated for their antiparasitic activity against four parasites in vitro. Two compounds showed promising activity against P. Falciparum, and molecular docking studies were conducted to understand the interactions between DNA minor groove and these compounds. All compounds exhibited theoretical ADME profiles conforming to Lipinski's and Ghose's restrictive rules.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Derya Osmaniye, Sevval Karaca, Berkant Kurban, Merve Baysal, Iqrar Ahmad, Harun Patel, Yusuf Ozkay, Zafer Asim Kaplancikli
Summary: Breast cancer is the most common cancer type among post-menopausal women. Drug resistance may develop in long-term drug use, leading to the need for new agents. This study synthesized new compounds and investigated their anticancer activities, aromatase inhibition, and DNA synthesis inhibition.
BIOORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ehsan Jahangirian, Jamil Zargan, Hodjattallah Rabbani, Javad Zamani
Summary: Bladder cancer, including muscle invasive and non-muscle invasive types, is a common worldwide cancer. Non-muscle invasive bladder cancer requires more therapy due to its higher recurrence rate and longer, more expensive care. Experimental studies have shown that crude scorpion venom and purified proteins and peptides can suppress cancer metastasis, inhibit cancer growth, stop cell cycle, and induce cell apoptosis. In this research, three novel peptides (P2, P3, P4) were discovered from scorpions and studied for their antimicrobial and anticancer properties. Peptides 2 and 3 showed the highest binding rate and were confirmed to penetrate the membrane of cancer cells and bacterial cells. QSAR analysis suggests that peptides 2 and 3 can act as anti-cancer and antimicrobial peptides.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Paris Jafari, Alexandre Luscher, Thissa Siriwardena, Murielle Michetti, Yok-Ai Que, Laurence G. Rahme, Jean-Louis Reymond, Wassim Raffoul, Christian Van Delden, Lee Ann Applegate, Thilo Kohler
Summary: In this article, a novel cell therapy formulation is developed to resist infections and inhibit the virulence pathways of pathogenic bacteria by incorporating antimicrobial peptide dendrimers and anti-quorum sensing compounds. The formulation includes live progenitor cells, exhibiting bactericidal and anti-virulence properties without compromising cell viability.
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
Chemistry, Multidisciplinary
David Kreutter, Philippe Schwaller, Jean-Louis Reymond
Summary: Training a molecular transformer model with multi-task transfer learning and combining extensive reaction and enzymatic transformation data allows for accurate prediction of the structure and stereochemistry of enzyme-catalyzed reaction products.