Article
Chemistry, Physical
S. R. Natesh, A. R. Hummels, J. R. Sachleben, T. R. Sosnick, K. F. Freed, J. F. Douglas, S. C. Meredith, E. J. Haddadian
Summary: Comparing three types of A beta(1-40) fibrils through molecular dynamics simulations, it was found that infinite fibrils were more stable than finite fibrils, brain-seeded and 2LMP fibrils allowed bidirectional water transport, and water diffusion in the fibril core involved two dynamic states. This study suggests that A beta fibrils could potentially act as nanotubes and have implications for A beta cytotoxicity due to the ability of oligomers to form abnormal water and ion channels in cell membranes.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Dusan Mrdenovic, Piotr Zarzycki, Marta Majewska, Izabela S. Pieta, Robert Nowakowski, Wlodzimierz Kutner, Jacek Lipkowski, Piotr Pieta
Summary: K162 inhibits the permeation of A beta Os-induced BLM, preserving BLM integrity. It modifies A beta aggregation by bypassing the formation of toxic A beta Os, producing only nontoxic A beta Ms, dimers, and fibrils. This unique mechanism may offer a new therapeutic strategy for AD.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Xingyue Li, Andrew L. Sabol, Patrick J. Salveson, James S. Nowick
Summary: Researchers have developed a new beta-turn template, (delta)MeOrn, which can induce a beta-hairpin conformation in peptides. This template demonstrates superior folding compared to (delta)Orn and is comparable to d-Pro-Gly.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Anna A. Rzepiela, Lauren A. Viarengo-Baker, Victor Tatarskii, Roman Kombarov, Adrian Whitty
Summary: This study measured the passive permeability of 3600 diverse macrocyclic compounds and used machine learning to analyze the results. It found that models incorporating selected properties based on the three-dimensional conformation could predict permeability with a high accuracy. The biased spatial distribution of polar versus nonpolar regions was found to be important for good permeability. Additionally, the study examined the effects of substructural elements on permeability, providing insights for designing macrocycles with high membrane permeability.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Beibei Li, Xu Ouyang, Zufang Ba, Yinyin Yang, Jingying Zhang, Hui Liu, Tianyue Zhang, Fangyan Zhang, Yun Zhang, Sanhu Gou, Jingman Ni
Summary: The study shows that the new antimicrobial peptides based on the beta-hairpin structure exhibit strong antibacterial activity with low toxicity, effectively inhibiting the development of drug-resistant bacteria. They have the potential to be alternative treatments for the antimicrobial resistance crisis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Engineering, Chemical
Song Liu, Guangyuan Zhou, Gongbi Cheng, Xiaokang Wang, Gongping Liu, Wanqin Jin
Summary: This review focuses on the separation of organic solvent mixtures using pervaporation and vapor permeation processes. These processes, compared with conventional distillation technology, offer lower energy consumption due to thermodynamic vapor-liquid equilibrium limitations. The review discusses different membrane materials and their separation mechanisms, such as affinity and size sieving, as well as the comparison with reverse osmosis process. The potential opportunities and challenges of applying advanced membrane materials for organic solvent mixtures separation are also discussed.
SEPARATION AND PURIFICATION TECHNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Andreia Boaro, Lucia Ageitos, Marcelo Der Torossian Torres, Esther Broset Blasco, Sebahat Oztekin, Cesar de la Fuente-Nunez
Summary: By utilizing structure-function-guided design, natural antimicrobial peptides (AMPs) derived from venom can be converted into α-helical AMPs with reduced toxicity. These synthetic derivatives exhibit potent antimicrobial activity against Gram-negative bacteria and demonstrate efficacy in a mouse model by significantly reducing bacterial loads. Furthermore, they do not readily induce bacterial resistance.
CELL REPORTS PHYSICAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Jillene Moxam, Sarah Naylon, Alexis D. Richaud, Guangkuan Zhao, Alberto Padilla, Stephane P. Roche
Summary: The recent trend of larger drug modalities has created a demand for novel compounds with high membrane permeability to inhibit intracellular protein-protein interactions. The development of large acyclic fi-hairpins has been lagging behind other designs. However, a study on a series of 26 beta-hairpins showed that their lipophilicity can be tuned to improve solubility and permeability.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Nanoscience & Nanotechnology
Marcus Vinicius Buri, Leticia Paulino Sperandio, Kamylla F. S. de Souza, Fernanda Antunes, Marina Mastelaro Rezende, Carina Mucciolo Melo, Maria A. S. Pinhal, Carlos C. Barros, David G. Fernig, Edwin A. Yates, Jaime S. Ide, Soraya S. Smaili, Karin A. Riske, Helena B. Nader, Ivarne Luis dos Santos Tersariol, Marcelo Andrade Lima, Wagner A. S. Judice, Antonio Miranda, Edgar J. Paredes-Gamero
Summary: The cytotoxic mode of action of four AMPs against a HeLa cell tumor model was discussed, revealing similarities in cell death induction such as annexin-V externalization, mitochondrial potential reduction, and membrane permeabilization. While responses to AMPs varied widely, endocytosis and GAG participation emerged as important and common mechanisms of cytotoxicity for beta-hairpin peptides.
ACS APPLIED BIO MATERIALS
(2021)
Article
Chemistry, Medicinal
Zhi Ma, Dong Zhang, Ziyi Cheng, Yandong Niu, Liangyu Kong, Zhaoxin Lu, Xiaomei Bie
Summary: The study synthesized a series of 10 short symmetrical beta-hairpin peptides, among which WK2 displayed the best selectivity towards Salmonella cells and exerted its antimicrobial activity through a membrane-lytic mechanism. Additionally, WK2 showed anti-inflammatory activity by suppressing the production of proinflammatory cytokines and demonstrated therapeutic effects against Salmonella infections in vivo.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Mithu Baidya, Madhu Chaturvedi, Hemlata Dwivedi-Agnihotri, Ashutosh Ranjan, Dominic Devost, Yoon Namkung, Tomasz Maciej Stepniewski, Shubhi Pandey, Minakshi Baruah, Bhanupriya Panigrahi, Parishmita Sarma, Manish K. Yadav, Jagannath Maharana, Ramanuj Banerjee, Kouki Kawakami, Asuka Inoue, Jana Selent, Stephane A. Laporte, Terence E. Hebert, Arun K. Shukla
Summary: This study reveals that synthetic antibodies can be used to modulate GPCR trafficking and signaling in live cells.
NATURE COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Zainularifeen Abduljaleel, Faisal A. Al-Allaf, Syed A. Aziz
Summary: The study focused on developing a peptide-based vaccine using molecular dynamics simulation to identify specific antibodies against SARS-nCoV-2. By constructing multiple antigenic epitope peptides, a highly antigenic vaccine with minimal allergic effects was developed. Further in vitro studies and clinical trials are needed to assess the efficacy of this vaccine.
BIO-DESIGN AND MANUFACTURING
(2021)
Article
Biochemistry & Molecular Biology
Laetitia F. Heid, Tatsiana Kupreichyk, Marie P. Schuetzmann, Walfried Schneider, Matthias Stoldt, Wolfgang Hoyer
Summary: Heterologous interactions between different amyloid-forming proteins can have a significant impact on disease-related amyloid formation. In this study, researchers tested how heterologous beta-hairpins derived from immunoglobulin light chains modulate the fibril formation of Parkinson's disease-associated protein alpha-synuclein. They found that the addition of these beta-hairpins affects the kinetics of alpha-synuclein aggregation, suggesting they support the nucleation of amyloid fibrils.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Shihao Pang, Jiawei Liu, Tianlong Li, Kai Ye, Zexin Yan, Li Zhao, Chunyan Bao
Summary: This study reports an artificial receptor that achieves controllable ON/OFF signal transduction through conformational changes, providing a new model for constructing artificial signal transduction systems.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Medicinal
Akshay Kapadia, Krishna K. Sharma, Indresh Kumar Maurya, Varinder Singh, Madhu Khullar, Rahul Jain
Summary: The synthesis of tetrapeptides based on the C-terminus fragment of A beta peptide showed promising protection against A beta aggregation-mediated neurotoxicity in PC-12 cells, with enhanced blood-brain barrier permeability and proteolytic stability. Structural insights and computational studies on ligand-A beta interactions offer new avenues for the advancement of peptide-derived therapeutics for AD.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Multidisciplinary Sciences
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: The question of how the same gene mutations can lead to both cancer and neurodevelopmental disorders has always been puzzling. This article reviews the literature and proposes that factors such as cell type-specific expression of the mutant protein, timing of activation, and the absolute number of molecules involved play key roles in determining the pathological phenotypes.
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: This article discusses the concept of productive signaling, including its definition, measurement, and determining factors. It highlights the importance of understanding signal propagation in diseases like cancer and neurodevelopmental disorders. The authors propose a framework for investigating signal transduction by defining cellular processes, conducting experimental measurements, and utilizing computational AI algorithms.
BIOPHYSICAL CHEMISTRY
(2022)
Article
Chemistry, Organic
Yixin Xie, Tania L. Lopez-Silva, Joel P. Schneider
Summary: We report a new positively charged azidoamino acid for strain-promoted azide-alkyne cycloaddition (SPAAC) applications that overcomes the solubility limitations of commonly used azidolysine, especially in systems with numerous ligation sites. The synthesized residue is compatible with Fmoc-based solid-phase peptide synthesis and exhibits efficient second-order rate constants in SPAAC ligations employing DBCO (0.34 M-1 s-1) and BCN (0.28 M-1 s-1).
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov
Summary: Bcr-Abl, a nonreceptor tyrosine kinase, plays a crucial role in leukemias, particularly chronic myeloid leukemia (CML). The fusion of Bcr and Abl leads to constitutive activation of Bcr-Abl. Oligomerization of Bcr-Abl is critical for its membrane clustering, MAPK signaling, and cell proliferation. Understanding the structural basis of Bcr-Abl oligomerization can guide the development of novel drugs targeting this process.
Article
Cell Biology
Chunyang Yi, Jiacheng He, Dan Huang, Yumiao Zhao, Chan Zhang, Xiyun Ye, Ying Huang, Ruth Nussinov, Junke Zheng, Mingyao Liu, Weiqiang Lu
Summary: Activation of the orphan GPCR GPR132 induces cell differentiation in acute myeloid leukemia (AML) and the natural product 8-gingerol is found to be a potential GPR132 agonist, promoting differentiation and reducing colony formation in AML cell lines.
CELL DEATH & DISEASE
(2022)
Letter
Oncology
Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
CANCER COMMUNICATIONS
(2023)
Article
Nanoscience & Nanotechnology
Yuji Yamada, Caleb F. F. Anderson, Joel P. P. Schneider
Summary: Peptide sequence periodicity is a useful design tool for generating functional peptide-based surface coatings. The de novo-designed peptide N-3-PEG-VK16 binds avidly to polystyrene surfaces, converting them into a wettable and electrostatically charged environment that facilitates cell attachment. This technology enables adhesion, expansion, and long-term culture of human induced pluripotent stem cells, as well as control of neurite outgrowth using functional ligands.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Review
Pharmacology & Pharmacy
Ruth Nussinov, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang
Summary: Drug discovery is a highly challenging and significant interdisciplinary aim. The success of AlphaFold, an AI-powered technology, has raised hopes for drug discovery, but its limitations need to be considered. Improving AlphaFold's performance in active state models can enhance the success rate of rational drug design.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Physical
Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
Summary: Kinase drug selectivity is a challenge in cancer research. Researchers propose a protocol to identify unique geometric features in the drug pocket that can distinguish one kinase from others. They analyze the structural principles of kinase drug selectivity using experimental structures and artificial intelligence. The results show that there are binary units in the kinome that can distinguish kinases from each other.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Article
Pharmacology & Pharmacy
Surabhi Kumari, Anuj Nehra, Kshitij Gupta, Anu Puri, Vinay Kumar, Krishna Pal Singh, Mukesh Kumar, Ashutosh Sharma
Summary: The authors developed biocompatible nano-vesicles using graphene oxide (GO) for the targeted release of chlorambucil (CHL) drugs in cancer cells. GO sheets were functionalized with folic acid (FA) molecules to improve controlled release and loading efficiency of CHL. The drug was loaded onto the GO surface through pi-pi stacking and hydrophobic interactions. In vitro release studies showed a pH-dependent release, with faster release at lower pH.
Review
Biophysics
Ruth Nussinov, Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Mingzhen Zhang, Yonglan Liu, Chung-Jung Tsai, Hyunbum Jang, Nurcan Tuncbag
Summary: Neurodevelopmental disorders (NDDs) and cancer have similarities in terms of proteins, pathways, and mutations, but have different clinical symptoms. However, individuals with NDDs have a higher likelihood of developing cancer later on. This review explores how shared features can result in different medical conditions and why having an NDD first can increase the chances of malignancy.
BIOPHYSICAL REVIEWS
(2023)
Article
Genetics & Heredity
Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov, Nurcan Tuncbag
Summary: Epidemiological studies show that individuals with neurodevelopmental disorders are more likely to develop certain types of cancer. While these disorders and cancer share proteins, pathways, and mutations, they differ in clinical outcomes. The key factor determining clinical outcome is signaling strength, with strong signaling promoting cell proliferation in cancer and moderate signaling affecting differentiation in neurodevelopmental disorders.
NPJ GENOMIC MEDICINE
(2023)
Review
Orthopedics
Arghya Kundu Choudhury, Kshitij Gupta, Sajid Ansari, Balgovind S. Raja, Souvik Paul, Roop Bhushan Kalia
Summary: This systematic review and meta-analysis found that the Attune knee system showed significant improvement in KSS scores and had favorable outcomes in terms of anterior knee pain and patellofemoral crepitus compared to the traditional PFC Sigma knee design. However, there were no significant differences in other outcome measures such as OKS and WOMAC scores, knee range of motion, patient satisfaction, and radiological outcomes.
ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY
(2023)
Article
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The propensities of protein conformations can predict cell function and suggest drug efficiency.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The sequence-structure-function paradigm in molecular biology has been updated to include the concept of conformational ensembles, recognizing that proteins are dynamic and constantly transitioning between different conformational states. The number and stability of these states are crucial for protein function. Understanding conformational propensities is essential for studying diverse systems and can provide insights into the dynamics of protein ensembles in cells.
RSC CHEMICAL BIOLOGY
(2023)