Article
Biochemistry & Molecular Biology
Panagiota S. Georgoulia, Sinisa Bjelic
Summary: This study investigates whether information contained in dimeric coiled coil folding energy landscapes can be used to predict protein binding interactions, showing a weak but existing correlation between the two. Further work is needed to improve the model presented in this research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Sicong Yao, Adam Moyer, Yiwu Zheng, Yang Shen, Xiaoting Meng, Chong Yuan, Yibing Zhao, Hongwei Yao, David Baker, Chuanliu Wu
Summary: Peptide heterodimers are functional macromolecules and molecular tools with wide applications in chemical and synthetic biology. In this study, the authors report the successful design, synthesis, and application of peptide heterodimers with mutual orthogonality through computational de novo designs and a directed disulfide pairing strategy. These heterodimers can be utilized as scaffolds for generating functional molecules, as well as chemical tools or building blocks for protein labeling and crosslinking hybrids.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Catherine Forest-Nault, Izel Koyuturk, Jimmy Gaudreault, Alex Pelletier, Denis L'Abbe, Brian Cass, Louis Bisson, Alina Burlacu, Laurence Delafosse, Matthew Stuible, Olivier Henry, Gregory De Crescenzo, Yves Durocher
Summary: This study compares the binding interactions of ACE2 with different RBD variants. Experiments conducted at 10 degrees Celsius reveal subtle differences between RBD mutants and provide important insights into ACE2 binding parameters.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Physical
Buddha R. Shrestha, Benoit Liberelle, Frederic Murschel, Enrico O. Purisima, Traian Sulea, Gregory De Crescenzo, Xavier Banquy
Summary: This study utilized the Surface Forces Apparatus to investigate the interaction mechanism between specific peptides forming a helical structure, revealing that binding initiates with weak interactions of distal heptads followed by an induced-fit process. Precise control of the distance between peptide-coated surfaces enabled quantitative monitoring of the evolution of binding energy.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Louise N. Slope, Oliver J. Daubney, Hannah Campbell, Scott A. White, Anna F. A. Peacock
Summary: This report highlights the unprecedented phenomenon of location-dependent and size-selective binding to lanthanide sites within miniature protein coiled coil scaffolds. The engineered binding sites show unusual selectivity for moderately large Ln(3+) ions, and it is demonstrated that this selectivity can be programmed into the sequence and manipulated by shifting the binding site. Experimental data, including X-ray crystal structures and CD studies, provide insights into the optimal radius of binding sites within the coiled coil scaffold, contributing to a better understanding of location-dependent metal selectivity in protein structures.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
News Item
Chemistry, Multidisciplinary
Giovanna Ghirlanda
Summary: Designing membrane proteins to function as ion channels is challenging, but peptides that self-assemble into water-soluble alpha-helical barrels offer a solution by lining the barrel interior with polar residues and the exterior with hydrophobic ones.
Article
Biochemistry & Molecular Biology
Rui Guo, Nairiti J. Sinha, Rajkumar Misra, Yao Tang, Matthew Langenstein, Kyunghee Kim, Jeffrey A. Fagan, Christopher J. Kloxin, Grethe Jensen, Darrin J. Pochan, Jeffery G. Saven
Summary: In this study, a set of computationally designed peptides with tunable charge were realized and characterized using experimental techniques.
Article
Chemistry, Multidisciplinary
Avanashiappan Nandakumar, Yoshihiro Ito, Motoki Ueda
Summary: A disulfide-tethered peptide-lipid conjugate can self-assemble into a homogeneously distributed peptide-lipid hybrid vesicle. Treatment with dithiothreitol causes the homogeneous peptide-lipid membrane to spontaneously separate into lipid-rich and peptide-rich domains, while the vesicle remains unchanged in size and shape. Membrane phase separation enhances temperature-dependent cargo release.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Physical
Andrea Hornemann, Diane M. Eichert, Arne Hoehl, Brigitte Tiersch, Gerhard Ulm, Maxim G. Ryadnov, Burkhard Beckhoff
Summary: Synchrotron radiation-based Fourier transform infrared spectroscopy is used to investigate the antimicrobial mechanisms of antimicrobial peptides (AMPs) by assessing the molecular specific variations in reconstituted phospholipid membranes. The study shows that temperature is a key factor in the activity of AMPs, providing direct evidence for membrane-induced and folding-mediated activity.
Article
Chemistry, Multidisciplinary
William M. Dawson, Freddie J. O. Martin, Guto G. Rhys, Kathryn L. Shelley, R. Leo Brady, Derek N. Woolfson
Summary: The rational design of linear peptides that assemble in water is challenging, as unique target structures must be encoded and alternative states avoided. Weak non-covalent forces that stabilize and discriminate between states present a challenge. However, progress has been made in rational de novo design for alpha-helical coiled-coil assemblies.
Article
Medicine, Research & Experimental
Seyed Farzad Baniahmad, Romane Oliverio, Ines Obregon-Gomez, Alma Robert, Anne E. G. Lenferink, Elena Pazos, Nick Virgilio, Xavier Banquy, Gregory De Crescenzo, Yves Durocher
Summary: Long-term delivery is a successful strategy to reduce adverse effects of mAb-based treatments. Macroporous hydrogels and affinity-based strategies are effective in sustained and localized delivery of mAbs. The Ecoil and Kcoil peptides have high-affinity binding and can be used for controlled release of Ecoil-tagged trastuzumab from macroporous hydrogels.
Article
Biochemistry & Molecular Biology
Cary R. Boyd-Shiwarski, Daniel J. Shiwarski, Shawn E. Griffiths, Rebecca T. Beacham, Logan Norrell, Daryl E. Morrison, Jun Wang, Jacob Mann, William Tennant, Eric N. Anderson, Jonathan Franks, Michael Calderon, Kelly A. Connolly, Muhammad Umar Cheema, Claire J. Weaver, Lubika J. Nkashama, Claire C. Weckerly, Katherine E. Querry, Udai Bhan Pandey, Christopher J. Donnelly, Dandan Sun, Aylin R. Rodan, Arohan R. Subramanya
Summary: When cells are exposed to hypertonicity, WNK kinases form condensates to activate ion influx, thereby restoring cell volume and ensuring cell survival.
Article
Multidisciplinary Sciences
Tae-Eun Kim, Kotaro Tsuboyama, Scott Houliston, Cydney M. Martell, Claire M. Phoumyvong, Alexander Lemak, Hugh K. Haddox, Cheryl H. Arrowsmith, Gabriel J. Rocklin
Summary: Designing new protein structures remains challenging, and our study successfully designed stable aPPa proteins through large-scale design and test cycles, shedding light on the biophysical determinants of folding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Huan Wang, Xinling Wang, Jiahui Li, Qing Li, Siliang Feng, Lu Lu, Chao Wang, Shibo Jiang
Summary: Both the deep pocket region and its neighboring subpocket site on the N-trimer of HIV-1 gp41 protein can be targeted for the development of HIV-1 entry inhibitors. This study reports the design of alpha-helical lipopeptides with non-native protein sequences as highly active HIV-1 fusion inhibitors that can occupy both the deep pocket and subpocket sites.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Dawei Xu, Samuel Lim, Yuhong Cao, Abner Abad, Aubrey Nayeon Kang, Douglas S. Clark
Summary: This study presents a filamentous chaperone-based protein hydrogel that can stabilize enzymes against thermal inactivation. The hydrogel backbone is composed of a thermostable chaperone protein, gamma-prefoldin (gamma PFD), which self-assembles into a fibrous structure. Engineered specific coiled-coil interactions in the wildtype gamma PFD trigger the formation of a cross-linked network of protein filaments, preserving the structure of the filamentous chaperone and enabling entrapped enzymes to retain greater activity after exposure to high temperatures.
CHEMICAL COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Sarah K. Madden, Aline Dantas de Araujo, Mara Gerhardt, David P. Fairlie, Jody M. Mason
Summary: Direct inhibition of c-Myc, a transcription factor overexpressed in many human cancers, has shown promising results in triggering tumor regression with reversible side effects. Challenges and lessons from current inhibitors are evaluated to explore future strategies for translating c-Myc inhibitors into clinical practice, such as miniaturisation of Omomyc and targeting E-box binding.
Article
Chemistry, Medicinal
Ferran Nadal-Bufi, Jody M. Mason, Lai Yue Chan, David J. Craik, Quentin Kaas, Sonia Troeira Henriques
Summary: Through rational and computer-based approaches, peptidic sequences with high affinity towards a beta-sheet region were identified and grafted into a cyclic cell-penetrating scaffold to inhibit LDH5 activity effectively. This approach of targeting an interface important for LDH5 function challenges the landscape of traditional small-molecule drug discovery programs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Neurosciences
Katriona L. Hole, Lydia E. Staniaszek, Gayathri Menon Balan, Jody M. Mason, Jon T. Brown, Robert J. Williams
Summary: Oral administration of EC reduces a specific phosphorylated form of tau in rTg4510 mice and inhibits its phosphorylation, independently of GSK3 beta regulation.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Richard M. Meade, Kathryn J. C. Watt, Robert J. Williams, Jody M. Mason
Summary: A peptide inhibitor was derived from a cell library screen to block aggregation of alpha-synuclein (α S) and its conversion into toxic species. Truncation and alanine scan analysis were used to determine inhibitory residues and improve peptide efficacy without disrupting α S lipid-binding. This work aims to develop a potent peptide antagonist of α S pathogenicity while preserving its native function.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
A. Kwok, I. S. Camacho, S. Winter, M. Knight, R. M. Meade, M. W. Van der Kamp, A. Turner, J. O'Hara, J. M. Mason, A. R. Jones, V. L. Arcus, C. R. Pudney
Summary: This study introduces a thermodynamic model of the tryptophan red edge excitation shift (REES) effect, which can quantify the relationship between the REES effect and protein flexibility. The model is applied to various examples of different scales, demonstrating its potential for experimental measurement of the protein REES effect and integration with biomolecular simulation to gain new insights.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kathryn J. C. Watt, Richard M. Meade, Robert J. Williams, Jody M. Mason
Summary: This study identified five peptides that have inhibitory effects on the aggregation of Parkinson's disease (PD) related protein variants. These peptides not only reduce the aggregation of PD-associated proteins, but also show the same efficacy when incubated with other variants. Additionally, the optimized peptide 4554W(N6A) is highly effective against wild-type protein and several single-point mutant forms, providing a suitable baseline for further PD therapeutic research.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
James T. Leech, Andrew Brennan, Nicola A. Don, Jody M. Mason, Neil M. Kad
Summary: The AP-1 transcription factor family plays a crucial role in regulating the cell cycle and has various functions in proliferation, differentiation, and stress response. This study shows that cFos can bind to DNA independently of cJun and can interact with DNA as both monomers and dimers.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jody M. Mason, Kathryn J. C. Watt, Richard M. Meade, Robert J. Williams
Summary: This article investigates the role of alpha-synuclein in synucleinopathies and explores the interplay between mutant alpha-synuclein and lipids.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Oncology
Emad Darvishi, Lila Ghamsari, Siok F. Leong, Ricardo Ramirez, Mark Koester, Erin Gallagher, Miao Yu, Jody M. Mason, Gene Merutka, Barry J. Kappel, Jim A. Rotolo
Summary: The study reveals the mechanism of action and antitumor activity of ST101, a novel peptide antagonist of C/EBP beta. ST101 inhibits dimerization of C/EBP beta and enhances its degradation, resulting in attenuation of transcription of C/EBP beta target genes and potent tumor-specific cytotoxic activity in various cancer cell lines. In mouse xenograft models, ST101 shows strong inhibition or regression of tumor growth, both as a single agent and in combination studies.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Ferran Nadal-Bufi, Lai Y. Chan, Hadi H. Mohammad, Jody M. Mason, Carlos Salomon, Andrew Lai, Erik W. Thompson, David J. Craik, Quentin Kaas, Sonia T. Henriques
Summary: This study reports the first peptide-based LDH5 inhibitor that can modulate cancer metabolism and kill glycolytic cancer cells. The study demonstrates the potential of using peptides as inhibitors of intracellular protein-protein interactions relevant for cancer pathways and shows that active peptides can be rationally designed to improve their cell permeation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Richard M. Meade, Scott G. Allen, Christopher Williams, T. M. Simon Tang, Matthew P. Crump, Jody M. Mason
Summary: Misfolding and aggregation of alpha-synuclein (aS) into toxic conformations is involved in neurodegenerative diseases. This study demonstrates that a peptide based on the first 25 residues of aS can inhibit its aggregation process, providing a potential route for the treatment or prevention of these diseases.
CELL REPORTS PHYSICAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Sarah K. Madden, Andrew Brennan, Jody M. Mason
Summary: Transcription factor dysregulation plays a key role in various diseases, and peptide-based inhibitors have shown potential in modulating protein-protein interactions. This study explores the use of a screening platform to identify a potent peptide inhibitor for the BZLF1 transcription factor. The library-derived peptide, AcidicW, demonstrates high stability and strong inhibition of BZLF1 function.
JOURNAL OF PEPTIDE SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Andrew Brennan, James T. Leech, Neil M. Kad, Jody M. Mason
Summary: The study developed a peptide antagonist that inhibits the activity of cJun through iterative truncation and side-chain cyclization. The resulting dual lactamized sequence is smaller and more stable in human serum, while maintaining high target affinity.
CELL REPORTS PHYSICAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Andrew Brennan, James T. Leech, Neil M. Kad, Jody M. Mason
Summary: This study reports the development of a high-throughput screening platform for deriving functional transcription factor antagonists. The platform, called transcription block survival (TBS), can prevent cell proliferation by blocking RNA polymerase gene transcription. It enables rapid screening of libraries to identify potentially therapeutically valuable sequences.
Article
Biochemistry & Molecular Biology
Miao Yu, Lila Ghamsari, Jim A. Rotolo, Barry J. Kappel, Jody M. Mason
Summary: The study focused on developing an antagonist selective for the Fra1 oncogenic transcriptional regulator using library design, computational screening, and intracellular screening. By reducing the library size and enriching for binders with specific criteria, the researchers identified a peptide (Fra1W) that exhibited specificity through a combination of hydrophobic and electrostatic contacts, showing high Fra1 affinity and selective binding. The multidisciplinary approach demonstrated a robust screening pipeline for generating target-specific hits and provided new insights into rational peptide design for novel bZIP family inhibitors.
RSC CHEMICAL BIOLOGY
(2021)