Article
Chemistry, Multidisciplinary
Jennifer R. Pace, Bryan J. Lampkin, Charles Abakah, Adam Moyer, Jiayuan Miao, Kirsten Deprey, Robert A. Cerulli, Yu-Shan Lin, James D. Baleja, David Baker, Joshua A. Kritzer
Summary: This study identified an optimal staple for antiparallel beta-strands using a novel computational strategy, and incorporated it into beta-hairpin peptides to create a unique kinked structure. The stapled hairpins demonstrated high structural stability in aqueous solution, excellent degradation resistance in cell lysates, and cytosolic penetration at micromolar concentrations. They also matched specific kinked hairpin motifs at protein-protein interaction interfaces, suggesting potential as starting points for developing inhibitors of cellular protein-protein interactions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Sunit Pal, Erode N. Prabhakaran
Summary: The study presents a solution-phase synthetic method for the rapid and cost-effective synthesis of high yields of STαH and EαH libraries, showing improved efficiency compared to conventional methods.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Motoharu Hirano, Chihiro Saito, Hidetomo Yokoo, Chihiro Goto, Ryuji Kawano, Takashi Misawa, Yosuke Demizu
Summary: Magainin 2, an antimicrobial peptide, relies on 17 amino acid residues for its antimicrobial activity, and derivatives with hydrocarbon stapling side chains can enhance this activity by stabilizing helical structures. The study found that hydrocarbon stapling significantly stabilizes helical structures of peptides, leading to improved antimicrobial activity without significant hemolytic effects. These findings suggest potential for developing novel antimicrobial agents based on Magainin 2 derivatives.
Article
Chemistry, Multidisciplinary
Jiang Liu, Peng Wang, Wei Zeng, Qi Lu, Qing Zhu
Summary: The study introduced a novel palladium-catalyzed Fujiwara-Moritani reaction for olefination of tryptophan residues without directing groups. This reaction is efficient for peptide modification, ligation, and peptide stapling.
CHEMICAL COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Sunit Pal
Summary: Protein-protein interactions (PPIs) involved in diseases can be modulated by chemically constrained peptides with proper helical conformation, which are capable of inducing future drug developments. Hydrogen-bond surrogate (HBS) is a well-known protocol that mimics helical surfaces in peptides, replacing the hydrogen bonding interaction with a covalent surrogate, and retaining the side-chain functionality intact for targeting multi-faced PPIs. This review focuses on the chemistry, biophysical characterizations, and biological applications of HBS-stabilized peptides, providing an overview of the HBS-model to attract chemical biologists for targeting multifaced 'difficult' PPIs.
Article
Chemistry, Multidisciplinary
Yuk-Cheung Chan, Marcus H. Sak, Scott A. Frank, Scott J. Miller
Summary: In this study, an organocatalytic enantioselective functionalization of heterocyclic carboxaldehydes via the Pictet-Spengler reaction was reported. A range of heterocycles could be tolerated by careful pairing of novel squaramide and Bronsted acid catalysts, leading to the synthesis of a series of heterocycle conjugated beta-(tetrahydro)carbolines with good yield and enantioselectivity. The utility of this method was demonstrated through the stereoselective preparation of pyridine-containing analogues of potent selective estrogen receptor downregulator and the U.S. FDA approved drug Tadalafil in three steps.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Dong-in Kim, Seong-jae Han, Yong-beom Lim
Summary: This study utilizes cyclic proteins and peptides to determine the maximum possible bending in the alpha-helix and finds that the radius of curvature is approximately 10 times smaller than those of typical alpha-helices found in natural proteins. This finding opens up possibilities for designing de novo peptides and proteins with unique structures and peculiar functions.
CHEMICAL COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Anton A. Komar
Summary: The study of peptides has helped understand the relationship between protein structure and activity. Short peptides can be used as therapeutic agents, but often have lower activity due to reduced structural organization, stability, and solubility. Various approaches, such as molecular stapling and peptide grafting, have been developed to improve the biological activity of short peptides by enforcing a more stable and active conformation.
Article
Chemistry, Physical
Eyber Domingos Alves, Douglas X. de Andrade, Agnaldo R. de Almeida, Guilherme Colherinhas
Summary: In this study, molecular dynamics simulations were used to investigate the structural and dynamic behavior of hydrogen bonds in A(6)X-type peptide structures at different temperatures. The results showed that the formation of hydrogen bonds is related to the mobility of peptides in the membrane and can impact the formation of hydration channels. The hydrogen bond network becomes more dynamic at higher temperatures, resulting in a more organized membrane structure with increased hydrogen bond density.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Article
Chemistry, Physical
H. N. Dilip, Debashree Chakraborty
Summary: Atomistic molecular dynamics simulations were conducted to investigate the structural and dynamical properties of water molecules around pre-assembled surfactant-like peptide (SLP) nanotubes in aqueous media. The study revealed differences in hydration levels and hydrogen bond lifetimes between charged and neutral SLPs, with the neutral SLPs having a less hydrated inner core. Moreover, protein-water hydrogen bond lifetimes were found to be longer for neutral analogues outside the pore due to more probable interactions with water molecules.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Biochemistry & Molecular Biology
Xiao Zhang, Zhiyang Zhang, Jia Guo, Jing Ma, Songqiang Xie, Yuan Zhao, Chaojie Wang
Summary: In this study, molecular dynamics simulations and various techniques were used to investigate the recognizing and binding mechanism of a peptide fragment from casein kinase II by OGT. Key residues like His496, His558, Thr633, Lys634, and Pro897 were found to play a dominant role in peptide stabilization through hydrogen bonds and sigma-pi interaction. Additionally, two delivery channels were identified, revealing the most favorable channel's transportation mode and characteristics.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Palanisamy Deepa, Duraisamy Thirumeignanam
Summary: This study investigates the significance of binding affinity between halogen and non-halogen derivatives of beta-d-Xylopyranose with amino acids of ruminant-beta-glycosidase. Through density functional theory analysis, it is shown that these derivatives exhibit strong interaction, providing clues for scientists to model new drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Agnaldo R. de Almeida, Guilherme Colherinhas, Douglas X. de Andrade
Summary: This study evaluates how the calculation method of Coulomb and van der Waals interactions, as well as their modifiers, affect the energetic and structural properties of A6H peptide nanomembranes. The use of cut-off as a basic method for calculating interactions results in more pronounced interactions, significantly affecting peptide nanomaterials. The modifier used strongly affects hydrogen bond lifetime and self-assembled structures with a highly aligned peptide beta-sheet structure.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Biochemistry & Molecular Biology
Carlos F. R. C. Guimaraes, Amanda S. Felix, Tiago A. S. Brandao, Marcelo P. P. Bemquerer, Dorila Pilo-Veloso, Rodrigo M. M. Verly, Jarbas M. M. Resende
Summary: Peptides are interesting alternatives for various applications, especially antimicrobial sequences due to antibiotic resistance. Although dimeric peptides show promise with strong biological activities and degradation resistance, there are relatively few studies due to synthesis obstacles. In this study, we investigate the dimerization of a cysteine-containing sequence to obtain a homodimeric antimicrobial peptide, and propose different dimerization protocols in selected environments. The results show that the reaction medium plays a major role in the formation of the disulfide bond.
Article
Biochemistry & Molecular Biology
Daniel Conde, Pablo F. Garrido, Martin Calvelo, Angel Pineiro, Rebeca Garcia-Fandino
Summary: This article investigates the behavior of self-assembled cyclic peptide nanotubes using molecular dynamics simulations and compares the performance of four different classical force fields in simulating these highly constrained peptides. Two methods to slow down the fastest degrees of freedom are also tested to improve simulation efficiency, and subtle differences are observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Vesna Stanojlovic, Anna Mueller, Ali Moazzam, Arthur Hinterholzer, Katarzyna Ozga, Lukasz Berlicki, Mario Schubert, Chiara Cabrele
Summary: The study introduces an acyclic but rigid β-hairpin scaffold XWXWXpPXK(/R)X(R) that exhibits high conformational stability, accommodating various side chains and showing versatility in accommodating different amino acid compositions.
Review
Chemistry, Inorganic & Nuclear
Stamatia Vassiliou, Aikaterini Pagoni, Ewelina Weglarz-Tomczak, Michal Talma, Wojciech Tabor, Agnieszka Grabowiecka, Lukasz Berlicki, Artur Mucha
Summary: The phosphinic acid functionality is a valuable scaffold for constructing biologically active compounds, particularly enzyme inhibitors. This article presents two recent achievements in using phosphinic acids as ligands for hydrolases, including the synthesis of a dipeptide analog inhibitor of metalloaminopeptidases and a catechol-based inhibitor of urease, as well as discussing the activity and mode of binding of phosphinic compounds to enzymes.
PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
(2022)
Article
Chemistry, Multidisciplinary
Monika Szefczyk, Katarzyna Ozga, Magda Drewniak-Switalska, Ewa Rudzinska-Szostak, Rafal Holubowicz, Andrzej Ozyhar, Lukasz Berlicki
Summary: The relationship between monomer structure and conformational properties at the oligomer level in foldamers remains a key issue in research. This study focused on the folding of peptidomimetic foldamers and factors affecting their conformational stability, specifically exploring the impact of peptide peripheral modification with trans- and cis-2-aminocyclopentanecarboxylic acid (ACPC) on the structure and stability of a model coiled-coil. The results showed significant differences in conformational stability between mutants containing trans-ACPC and cis-ACPC, despite differing only in one peripheral stereogenic center.
Article
Chemistry, Medicinal
Agnieszka Ciesiolkiewicz, Juan Lizandra Perez, Lukasz Berlicki
Summary: This review presents methodologies for the development of miniprotein scaffolds and the construction of biologically active miniproteins. It highlights the potential of miniproteins as drug candidates by virtue of their well-defined structure and good synthetic availability, particularly for targeting previously considered undruggable targets.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Review
Chemistry, Multidisciplinary
Saurabh Loharch, Lukasz Berlicki
Summary: This review provides current knowledge on the structures, activity, and biological importance of bacterial ureases, and discusses the structure-based design of several classes of bacterial urease inhibitors. The study suggests that urease inhibitors may have potential therapeutic effects against Helicobacter pylori and Proteus spp. infections.
Article
Biochemistry & Molecular Biology
Maciej Bladowski, Ewa Szahidewicz-Krupska, Jerzy Wisniewski, Paulina Fortuna, Justyna Chojdak-Lukasiewicz, Slawomir Budrewicz, Mariusz Fleszar, Adrian Doroszko
Summary: This study aimed to analyze the differences in the expression of the nitric oxide metabolic pathway in platelets and plasma between ischemic stroke patients and non-stroke individuals. It also investigated the relationship between these parameters and platelet aggregation. The results showed that stroke patients had higher levels of NOS inhibitors in platelets, and stroke management increased the bioavailability of nitric oxide in platelets.
Review
Peripheral Vascular Disease
Edyta Sutkowska, Michal Fulek, Katarzyna Fulek, Paulina Fortuna, Katarzyna Madziarska
Summary: All circumstances influencing Virchow's Triad elements can increase the risk of venous thromboembolism, such as nephrotic syndrome. Mechanical anticoagulant prophylaxis should be implemented in nephrotic syndrome patients to reduce the risk of VTE and improve quality of life.
Article
Medicine, Research & Experimental
Patrycja Lesnik, Lidia Lysenko, Mariusz G. Fleszar, Paulina Fortuna, Ewa Woznica-Niesobska, Magdalena Mierzchala-Pasierb, Jaroslaw Janc
Summary: This study used LC-MS/MS to determine the serum concentrations of selected amino acids and amines in patients with AKI during sepsis. The results showed that the DMA level was significantly higher in AKI patients. No significant differences were observed for the other molecules.
MEDICAL SCIENCE MONITOR
(2022)
Article
Chemistry, Medicinal
Katarzyna Macegoniuk, Wojciech Tabor, Luca Mazzei, Michele Cianci, Miroslaw Giurg, Kamila Olech, Malgorzata Burda-Grabowska, Rafal Kaleta, Agnieszka Grabowiecka, Artur Mucha, Stefano Ciurli, Lukasz Berlicki
Summary: Screening of 25 analogs of Ebselen led to the discovery of highly potent inhibitors of Sporosarcina pasteurii urease, with a Ki value in a low picomolar range. The exceptional activity was attributed to the presence of a dihalogenated phenyl ring, which increased pi-pi and pi-cation interactions. Biological studies showed good potency for monosubstituted N-phenyl derivatives in inhibiting ureolysis in Proteus mirabilis cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Letter
Psychiatry
Blazej Misiak, Tomasz Bielawski, Jerzy Samochowiec, Agnieszka Samochowiec, Mariusz G. Fleszar, Paulina Fortuna, Bogna Kosyk, Dorota Frydecka
SCHIZOPHRENIA RESEARCH
(2023)
Article
Chemistry, Physical
Katarzyna Ozga, Lukasz Berlicki
Summary: An artificial retroaldolase was developed using a miniprotein derived from MvaT protein. Rational optimization of activity was performed by modifying the active motif, active site structure, and surface charge distribution, showing the potential for obtaining an effective enzyme-like catalyst and tuning its efficiency by optimizing surface charge distribution.
Article
Environmental Sciences
Jakub Mochol, Jakub Gawrys, Ewa Szahidewicz-Krupska, Jerzy Wisniewski, Paulina Fortuna, Piotr Rola, Helena Martynowicz, Adrian Doroszko
Summary: This study aimed to investigate the role of erythrocytes in the storage and accumulation of ADMA in patients with OSA. The results showed that the erythrocyte concentration of ADMA was lower than in plasma, and CPAP treatment did not change the levels of NO metabolites in the erythrocytes.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Chemistry, Medicinal
Marta Maslanka, Wojciech Tabor, Pawel Krzyzek, Agnieszka Grabowiecka, Lukasz Berlicki, Artur Mucha
Summary: Catechols have been identified as potent covalent inhibitors of ureases by modifying cysteine residues at the active site. We synthesized novel catecholic derivatives with carboxylate and phosphonic/phosphinic groups, which demonstrated expanded specific interactions. The compound 2-(3,4-dihydroxyphenyl)-3-phosphonopropionic acid (15) exhibited significant anti-urease potential with a Ki value of 2.36 μM and displayed antiureolytic effects in live Helicobacter pylori cells at a submicromolar concentration (IC50 = 0.75 μM). Molecular modeling revealed its binding to the active site through electrostatic and hydrogen bond interactions. These catecholic phosphonic acids exhibited specific antiureolytic activity without cytotoxicity to eukaryotic cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Wojciech Tabor, Aikaterini Katsogiannou, Danai Karta, Evgenia Andrianopoulou, Lukasz Berlicki, Stamatia Vassiliou, Agnieszka Grabowiecka
Summary: A series of thiourea-based urease inhibitors were synthesized and evaluated for their inhibitory activity against bacterial urease enzymes and whole cells. The inhibitors included diverse structural compounds such as thiosemicarbazones, thiocarbohydrazones, benzyl-substituted thiazolyl thioureas, 1H-pyrazole-1-carbothioamides, and dihydropirimidine-2(1H)-thiones. In kinetic studies, low micromolar inhibitors were identified within each structural group. Modeling studies showed the coordination of sulfur ions and hydrogen bonds in the active site of the enzymes. Whole-cell studies demonstrated the activity of these compounds against both Gram-positive and Gram-negative microorganisms. The inhibition of ureolysis in a pathogenic strain of P. mirabilis was particularly noteworthy.
Article
Chemistry, Physical
Monika Szefczyk, Natalia Szulc, Marlena Gasior-Glogowska, Dominika Bystranowska, Andrzej Zak, Andrzej Sikora, Oliwia Polanska, Andrzej Ozyhar, Lukasz Berlicki
Summary: In this paper, a hierarchical approach for constructing nanofibrils based on alpha,beta-peptide foldamers is proposed as a rational method for designing novel self-assembled nanomaterials. The incorporation of a specific amino acid residue resulted in the formation of helical foldamers, which was confirmed by spectroscopic techniques. The obtained alpha,beta-peptides showed a strong tendency to aggregate and form self-assembled nanostructures, as revealed by assays and microscopy. The location of the beta-amino acid in the coiled-coil structure affected the secondary structure and morphology of the self-assembled nanostructures.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)