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
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
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
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
Multidisciplinary Sciences
Kobe Janssen, Filip Claes, Dido Van de Velde, Vanessa L. Wehbi, Bert Houben, Yulia Lampi, Mieke Nys, Laleh Khodaparast, Ladan Khodaparast, Nikolaos Louros, Rob van der Kant, Joffre Verniers, Teresa Garcia, Meine Ramakers, Katerina Konstantoulea, Katerina Maragkou, Ramon Duran-Romana, Monica Musteanu, Mariano Barbacid, Bernard Scorneaux, Els Beirnaert, Joost Schymkowitz, Frederic Rousseau
Summary: Mutant KRAS is a challenging target for classical small molecule drugs, but this study shows that its misfolding can be induced by synthetic peptides derived from specific regions of the oncoprotein. These peptides were able to inhibit the function of mutant KRAS and showed antiproliferative activity against cancer cells. The findings provide proof-of-concept for exploiting the intrinsic misfolding propensity of KRAS as a therapeutic strategy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
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
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)
Article
Chemistry, Physical
Wenbo Zhang, Mingwei Liu, Lanlan Yu, Shanshan Mo, Zhun Deng, Shuli Liu, Yanlian Yang, Chen Wang, Chenxuan Wang
Summary: This study demonstrates the contribution of various noncovalent interactions to supramolecular assembly by investigating the self-assembly of peptides.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
George Chao, Timothy M. Wannier, Clair Gutierrez, Nathaniel C. Borders, Evan Appleton, Anjali Chadha, Tina Lebar, George M. Church
Summary: Cell-cell interactions are crucial in tissue engineering and immune cell targeting. Traditional cell adhesion molecules have limitations, but this study presents a novel approach of engineering synthetic cell adhesion molecules using coiled-coil peptides on the cell surface, which has been successfully applied in various multicellular engineering applications.
Article
Multidisciplinary Sciences
Kimberly Jia Yi Low, Anandalakshmi Venkatraman, Jodhbir S. Mehta, Konstantin Pervushin
Summary: Protein aggregation and deposition in the form of amyloid fibrils is a characteristic feature of amyloid diseases. While most research focuses on inhibiting amyloid formation, it is equally important to understand the disaggregation mechanisms and their potential therapeutic applications. This review compiles the known mechanisms of amyloid disaggregation and explores the use of disaggregases for treating amyloidosis.
JOURNAL OF ADVANCED RESEARCH
(2022)
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
Multidisciplinary Sciences
Raphael D. Teixeira, Fabian Holzschuh, Tilman Schirmer
Summary: This passage discusses how diguanylate cyclases synthesising the bacterial second messenger c-di-GMP are regulated by sensory input domains and reveals a key step in the activation mechanism.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Anett Hauser, Eleftheria Poulou, Fabian Mueller, Peter Schmieder, Christian P. R. Hackenberger
Summary: The cover of this issue features an image of a phospho-lysine peptide mimic, reflecting a phosphorylated lysine but not identical. Visit the website 10.1002/chem.202003947 for the full article.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Anselm F. L. Schneider, Laila S. Benz, Martin Lehmann, Christian P. R. Hackenberger
Summary: Super-resolution microscopy in living cells can be enhanced by the use of engineered cell-permeable and highly fluorescent nanobodies as intracellular targeting agents. These semi-synthetic nanobodies, with bright fluorescent signals achieved through intramolecular photostabilization, have a cleavable cell-penetrating peptide for efficient cellular entry. Their utility has been demonstrated in functional analysis through monitoring cell division and DNA replication via confocal and STED microscopy.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Christian E. Stieger, Luise Franz, Frieder Koerlin, Christian P. R. Hackenberger
Summary: Diethynyl phosphinates are developed as bisfunctional electrophiles for site-selective modification of peptides, proteins, and antibodies. The obtained conjugates are stable in human plasma and in the presence of small thiols. This method is suitable for generating functional protein conjugates, including homogeneously rebridged antibodies that remain specific for their target.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Marc-Andre Kasper, Lukas Lassak, Annette M. Vogl, Isabelle Mai, Jonas Helma, Dominik Schumacher, Christian P. R. Hackenberger
Summary: Bis-ethynylphosphonamidates allow for a simple chemoselective addition of two thiol-containing modules in a row. Functional O-substituents with tunable hydrophilicity enable further subsequent conjugations, facilitating the construction of protein-protein conjugates. The increased spacer length between the ethynylphosphonamidates simplifies the formation of a conjugate from bulky proteins.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Carolina Sarto, Sebastian Florez-Rueda, Mehrnoosh Arrar, Christian P. R. Hackenberger, Daniel Lauster, Santiago Di Lella
Summary: This study determined the binding affinity between ACE2-derived peptides and the RBD of SARS-CoV-2, and identified critical peptide anchors. New ACE2-derived peptides were developed based on interface analysis, and a correlation between helicity and binding affinity was found. Additionally, a cyclized version of p6 with increased helicity and reduced K (D) value was created.
BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Lutz Adam, Eva Muller, Kai Ludwig, Simon Klenk, Daniel Lauster, Susanne Liese, Andreas Herrmann, Christian P. R. Hackenberger
Summary: The conjugation of virus-binding ligands to multivalent carriers is an effective strategy to inhibit viral entry into host cells. Even partially sialylated ligands can retain their inhibitory effect, and carriers carrying two different ligand-linker structures showed higher viral inhibition.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Pascal M. Engelhardt, Sebastian Florez-Rueda, Marco Drexelius, Joerg-Martin Neudoerfl, Daniel Lauster, Christian P. R. Hackenberger, Ronald Kuehne, Ines Neundorf, Hans-Guenther Schmalz
Summary: Researchers used a rigidified diproline-derived module ProM-5 to induce alpha helicity in ACE2-inspired peptide sequences. They found increased alpha helicity when non-binding amino acids were replaced with alanine. The binding affinities of the peptides towards the spike protein showed that the alpha-helical content had only a subtle influence, with one specific peptide displaying a strong binding affinity.
Article
Chemistry, Multidisciplinary
Abhishek Saha, Shaswati Mandal, Jan Vincent V. Arafiles, Jacobo Gomez-Gonzalez, Christian P. R. Hackenberger, Ashraf Brik
Summary: By studying DABCYL-modified cR10 peptides and their derivatives, it was found that the efficiency of Ub cargo entering living cells can be significantly improved, which is of great research value.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Multidisciplinary
Eleftheria Poulou, Christian P. R. Hackenberger
Summary: This review highlights the groundbreaking discoveries and applications of Staudinger reactions in the molecular life sciences, including its engineering as a bioorthogonal reaction and its recent applications in generating next-generation biopharmaceuticals through modern bioconjugation methods.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Don S. Munasinghe, Marc-Andre Kasper, Radomir Jasinski, Karolina Kula, Marcin Palusiak, Malgorzata Celeda, Grzegorz Mloston, Christian P. R. Hackenberger
Summary: By utilizing the reactivity of ethynyl-phosphonites, novel P(V)-containing five-membered heterocycles were synthesized via (3+2)-cyclization reactions with aldehydes or cycloaliphatic thioketones, yielding satisfactory to excellent yields. The reactions with thioketones proceeded smoothly at room temperature without any catalyst, while the conversions with aldehydes required the addition of triethylamine as a base. A step-wise (3+2)-cyclization mechanism for the formation of the 1,3-thiaphosphole ring was proposed based on DFT quantum chemical calculations. This study introduces new cyclization reactions using unsaturated phosphonites as central synthetic building blocks to access stable phosphorus-containing heterocycles with unexplored potential in the molecular sciences.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Jan Vincent V. Arafiles, Jonathan Franke, Luise Franz, Jacobo Gomez-Gonzalez, Kristin Kemnitz-Hassanin, Christian P. R. Hackenberger
Summary: This study presents a powerful and efficient strategy for the intracellular delivery of functional cargoes. By increasing the retention on the cellular membrane, the authors found that CPP additives with a hydrophobic peptide sequence can enhance the uptake of protein cargoes without causing cytotoxicity. The results provide important design principles for cell-surface-retained CPP additives and demonstrate the potential of hydrophobic CPP additives in delivering fluorescent proteins and functional macrocyclic peptides.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Jacob Gorenflos L. Lopez, Peter Schmieder, Kristin Kemnitz-Hassanin, Hatice Ceyda Asikoglu, Arif Celik, Christian E. Stieger, Dorothea Fiedler, Stephan Hinderlich, Christian P. R. Hackenberger
Summary: This study introduces a real-time assay to monitor different enzymatic steps of sialic acid biosynthesis. The NMR techniques used in this study allow for the identification of characteristic signals and suggest that MNK phosphorylation reaction is exclusive for N-acetylmannosamine generated by GNE. Competition experiments reveal the preference of an N-acetylglucosamine-preferring kinase in the phosphorylation process.
Article
Chemistry, Multidisciplinary
Sarah Hansen, Jan Vincent V. Arafiles, Philipp Ochtrop, Christian P. R. Hackenberger
Summary: We report an efficient method to selectively install electrophilic ethynyl-phosphonamidates on peptides during solid phase peptide synthesis. The synthesized peptidic compounds, including a cell-penetrating peptide, showed high efficiency as an additive for cellular delivery of proteins.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Bingjia Yan, Wenyi Li, Christian P. R. Hackenberger
Summary: This report introduces a novel building block for solid phase synthesis of beta-linked O-GlcNAcylated peptides, which carries acid labile silyl ether protecting groups. These protecting groups can be easily removed under TFA-mediated peptide cleavage conditions, leading to fewer synthetic steps and no intermediate purification compared to other protecting group strategies.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yerin Park, Alice L. Baumann, Hyejin Moon, Stephen Byrne, Marc-Andre Kasper, Songhwan Hwang, Han Sun, Mu-Hyun Baik, Christian P. R. Hackenberger
Summary: This study investigated the reactivity of P(v) electrophiles towards thiols, revealing the influence of vinyl and ethynyl substituents on overall reactivity, and the key role of hyperconjugation in stabilizing intermediates. The study also provided a detailed mechanistic picture for designing P(v)-based electrophiles with fine-tuned reactivity profiles.