A5057711095- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Carbohydrate Chemistry and Synthesis
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Nanoplatforms for cancer theranostics
- RNA modifications and cancer
- SARS-CoV-2 detection and testing
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- Photochemistry and Electron Transfer Studies
- DNA and Nucleic Acid Chemistry
- Microtubule and mitosis dynamics
- NF-κB Signaling Pathways
- vaccines and immunoinformatics approaches
- Advanced Proteomics Techniques and Applications
- DNA Repair Mechanisms
Tel Aviv University
2022-2025
Technion – Israel Institute of Technology
2015-2023
Exact Sciences (United States)
2023
Massachusetts Institute of Technology
2020-2021
Ben-Gurion University of the Negev
2013-2015
The acetamidomethyl (Acm) moiety is a widely used cysteine protecting group for the chemical synthesis and semisynthesis of peptide proteins. However, its removal not straightforward requires harsh reaction conditions additional purification steps before after step, which extends synthetic process reduces overall yield. To overcome these shortcomings, method rapid efficient Acm using Pd(II) complexes in aqueous medium reported. We show, first time, assembly three fragments one-pot fashion by...
Facilitating the process of chemical protein synthesis is an important goal in order to enable efficient preparation large and novel analogues. Native ligation, which widely used semisynthesis proteins, has been going through several developments expedite synthetic obtain target high yield. A key aspect this approach utilization protecting groups for N-terminal Cys middle fragments, bear simultaneously two reactive groups, i.e., C-terminal thioester. Despite progress area, as demonstrated...
Abstract Organic chemistry allows for the modification and chemical preparation of protein analogues various studies. The thiolate side chain Cys residue has been a key functionality in these ventures. In order to generate complex molecular targets, there is particular need incorporate orthogonal protecting groups thiolated amino acids control directionality synthesis site. Here, we demonstrate tuning palladium chemoselectivity aqueous medium on-demand deprotection several Cys-protecting...
The β-coronavirus SARS-CoV-2 has caused a global pandemic. Affinity reagents targeting the spike protein are of interest for development therapeutics and diagnostics. We used affinity selection–mass spectrometry rapid discovery synthetic high-affinity peptide binders receptor binding domain (RBD) protein. From library screening with 800 million peptides, we identified three sequences nanomolar affinities (dissociation constants Kd = 80–970 nM) RBD selectivity over human serum proteins....
Abstract The chemical synthesis of a protein from four fragments or more applying native ligation could be achieved stepwise, in one‐pot, convergently, on solid support. With the increasing demands to highly complex targets, examining these approaches becomes essential achieve efficient synthesis. Different synthetic strategies are compared for preparation H2B having different post‐translational modifications. analogues include that is ubiquitinated at Lys34, Lys120, glycosylated Ser112, and...
Reversible attachment of solubilizing tags to hydrophobic peptides facilitate their purification and ligation is an essential yet challenging task in chemical protein synthesis. The efficient palladium-assisted removal the tag linked Cys side chain reported. strategy was applied for preparation histone H4 from two fragments via one-pot operation ligation, tag, desulfurization.
Abstract Monoubiquitination of histone H2B plays a central role in transcription activation and is required for downstream histone‐methylation events. Deubiquitination by the Spt‐Ada‐Gcn5 acetyltransferase (SAGA) coactivator complex regulated recently discovered mark, phosphorylated H2AY57 (H2AY57p), which inhibits deubiquitination SAGA as well restricting demethylation H3 increasing its acetylation. Evidence effect H2AY57p, however, was indirect investigated vivo monitoring effects chemical...
Abstract The acetamidomethyl (Acm) moiety is a widely used cysteine protecting group for the chemical synthesis and semisynthesis of peptide proteins. However, its removal not straightforward requires harsh reaction conditions additional purification steps before after step, which extends synthetic process reduces overall yield. To overcome these shortcomings, method rapid efficient Acm using Pd II complexes in aqueous medium reported. We show, first time, assembly three fragments one‐pot...
Transcription factors (TF), such as Myc, are proteins implicated in disease pathogenesis, with dysregulation of Myc expression 50% all human cancers. Still, targeting remains a challenge due to the lack small molecule binding pockets tertiary structure. Here, we report synthetic covalently linked TF mimetics that inhibit oncogenic Myc-driven transcription by antagonistic target DNA-binding site. We combined automated flow peptide chemistry palladium(II) oxidative addition complexes (OACs)...
Synthetic strategies to assemble peptide fragments are in high demand access homogeneous proteins for various applications. Here, we combined native chemical ligation (NCL) and Pd-mediated Cys arylation enable practical at aromatic junctions. The utility of one-pot NCL S-arylation the Phe Tyr junctions was demonstrated employed rapid synthesis DNA-binding domains transcription factors Myc Max. Organometallic palladium reagents coupled with enabled a strategy peptides
Chemical protein synthesis provides a powerful means to prepare novel modified proteins with precision down the atomic level, enabling an unprecedented opportunity understand fundamental biological processes. Of particular interest is process of gene expression, orchestrated through interactions between transcription factors (TFs) and DNA. Here, we combined chemical high-throughput screening technology decipher role post-translational modifications (PTMs), e.g., Lys-acetylation on DNA...
Nature employs proteins as molecular machines to orchestrate numerous intricate biological processes. Natural are primarily synthesized from 22 proteinogenic amino acids. In principle, developing abiotic with novel non-proteinogenic residues can expand their functional space, enabling the discovery of new reactivities not found in nature. Here, we combined a rational design total synthesis develop derived natural transcription factors (TFs). We library TFs using solid-phase and native...
We report a one-pot total synthesis of the transcription factor Max in seven consecutive steps, starting from three peptide segments and employing native chemical ligation. The developed facilitates generation homogeneous analogues bearing defined transformations within hours excellent yields, enabling us to probe effect crosstalk between Ser-phosphorylation Lys-acetylation on function. Our findings reveal that these post-translational modifications significantly inhibit DNA-binding...
Presented here is a solid phase chemical ligation strategy employing native and the commercially available Rink-amide linker as key element in our approach. The method was applied for synthesis of histone H2B, which sets ground rapid preparation posttranslationally modified analogues this protein.
Abstract In den letzten Jahren hat das Gebiet der ortsspezifischen Modifizierung von Proteinen aufgrund seiner Bedeutung für die Entwicklung neuer Therapeutika, Verständnis biochemischer und zellulärer Verhaltensweisen verwandte Forschungsgebiete erhebliche Beachtung gefunden. Durch Gegenwart einer großen Anzahl reaktiver funktioneller Gruppen im betreffenden Protein in zellulären Umgebung stellt spezifischen Stelle eine besonders schwierige Aufgabe dar. Mit ausgeklügelter chemischer...
The design and synthesis of biomolecules that are responsive to external stimuli is great interest in various research areas, such as the preparation smart biomaterial chemical biology. Polypeptide backbone disassembly a response particular stimulus interest, it leads complete loss protein tertiary structure and, result, function. In this study, strategy based on palladium-assisted efficient cleavage thiazolidine linkage peptides proteins was developed. Using fluorescence-based assay,...
Dysregulation of the transcription factor MYC is involved in many human cancers. The dimeric complexes MYC/MAX and MAX/MAX activate or inhibit, respectively, gene upon binding to same enhancer box DNA. Targeting these cancer a long-standing challenge. Inspired by inhibitory activity dimer, we engineered covalently linked, synthetic homo- heterodimeric protein attenuate oncogenic MYC-driven transcription. We prepared covalent (∼20 kDa, 167–231 residues) single shot via parallel automated flow...
The chemical synthesis of site-specifically modified transcription factors (TFs) is a powerful method to investigate how post-translational modifications (PTMs) influence TF-DNA interactions and impact gene expression. Among these TFs, Max plays pivotal role in controlling the expression 15 % genome. activity regulated by PTMs; Ser-phosphorylation at N-terminus considered one key regulatory mechanisms. In this study, we developed practical synthetic strategy prepare homogeneous full-length...
Site-selective functionalization strategies are in high demand to prepare well-defined homogeneous proteins for basic research and biomedical applications. In this regard, cysteine-based reactions have enabled a broad set of transformations produce modified various However, these approaches were mainly employed modify single reactive site with specific transformation. Achieving selectivity or multiple transformations, essential preparing complex biomolecules, remains challenging. Herein we...
Posttranslational modifications (PTMs) of proteins play central roles in regulating the protein structure, interactome, and functions. A notable modification site is aromatic side chain Tyr, which undergoes such as phosphorylation nitration. Despite biological physiological importance Tyr-PTMs, our current understanding mechanisms by these contribute to human health disease remains incomplete. This knowledge gap arises from absence natural amino acids that can mimic PTMs lack synthetic tools...