A5064056983- RNA and protein synthesis mechanisms
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Origins and Evolution of Life
- Bacterial Genetics and Biotechnology
- DNA and Nucleic Acid Chemistry
- Carbohydrate Chemistry and Synthesis
- RNA modifications and cancer
- Fluorine in Organic Chemistry
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- Antimicrobial Peptides and Activities
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Global Peace and Security Dynamics
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Cancer-related gene regulation
- Microbial Metabolites in Food Biotechnology
- Antibiotic Resistance in Bacteria
- Immune Response and Inflammation
- Advanced biosensing and bioanalysis techniques
- Advanced Proteomics Techniques and Applications
- Political and Social Dynamics in Chile and Latin America
- Probiotics and Fermented Foods
Howard Hughes Medical Institute
2018-2023
Massachusetts General Hospital
2018-2023
Harvard University
2019-2023
University of Vienna
2023
University of Oxford
2016-2021
Justus-Liebig-Universität Gießen
2021
University of Dundee
2021
University College Cork
2021
University of London
2021
University of Edinburgh
2021
Posttranslational modification of proteins expands their structural and functional capabilities beyond those directly specified by the genetic code. However, vast diversity chemically plausible (including unnatural but functionally relevant) side chains is not readily accessible. We describe C (sp3)-C (sp3) bond-forming reactions on under biocompatible conditions, which exploit unusual carbon free-radical chemistry, use them to form Cβ-Cγ bonds with altered chains. demonstrate how these...
A radical lipidation: Application of a novel thiol–ene lipidation enables the one-step synthesis self-adjuvanting antigenic peptides as vaccine candidates. The resultant monoacyl lipopeptides are shown to activate monocytes in robust manner.
Non-enzymatic RNA self-replication is integral to the emergence of 'RNA World'. Despite considerable progress in non-enzymatic template copying, demonstrating a full replication cycle remains challenging due difficulty separating strands product duplex. Here, we report prebiotically plausible approach strand displacement synthesis which short 'invader' oligonucleotides unwind an duplex through toehold/branch migration mechanism, allowing primer extension on that was previously occupied by...
Replacing the <italic>O</italic>-linked saccharide in bacteriocin glycocin F with an <italic>S</italic>-linked version results a peptidomimetic that increases bacteriostatic effect.
A key challenge in origin-of-life research is the identification of plausible conditions that facilitate multiple steps along pathway from chemistry to biology. The incompatibility nucleotide activation and nonenzymatic template-directed RNA copying has hindered attempts define such a pathway. Here, we show adding heteroaromatic small molecules reaction network facilitates situ phosphate under compatible with copying, allowing both reactions take place same mixture. This achieved using...
Aminoacylated transfer RNAs, which harbor a covalent linkage between amino acids and RNA, are universally conserved feature of life. Because they essential substrates for ribosomal translation, aminoacylated oligonucleotides must have been present in the RNA world prior to evolution ribosome. One possibility we exploring is that aminoacyl ester served another function before being recruited protein synthesis. The nonenzymatic assembly ribozymes from short oligomers under realistic conditions...
Abstract The first total synthesis of glycocin F, a uniquely diglycosylated antimicrobial peptide bearing rare S‐linked N ‐acetylglucosamine (GlcNAc) moiety in addition to an O‐linked GlcNAc, has been accomplished using native chemical ligation strategy. synthetic and naturally occurring peptides were compared by HPLC, mass spectrometry, NMR CD spectroscopy, their stability towards chymotrypsin digestion activity measured. This is the comprehensive structural functional comparison with...
Six analogues of the potent lipopeptide antibiotic, teixobactin were prepared by Fmoc SPPS and their activities examined against Gram positive bacteria.
Achieving multiple cycles of RNA replication within a model protocell would be critical step toward demonstrating path from prebiotic chemistry to cellular biology. Any for early life based on an "RNA world" must account strand cleavage and hydrolysis, which degrade primitive genetic information lead accumulation truncated, phosphate-terminated strands. We show here that the phosphodiester backbone is not end point replication. Instead, 3′-phosphate-terminated strands can participate in...
Aminoacylated tRNAs are the substrates for ribosomal protein synthesis in all branches of life, implying an ancient origin aminoacylation chemistry. In 1970s, Orgel and colleagues reported potentially prebiotic routes to aminoacylated nucleotides their RNA-templated condensation form amino acid-bridged dinucleotides. However, it is unclear whether such reactions would have aided or impeded non-enzymatic RNA replication. Determining RNAs could been advantageous evolution prior emergence...
Non-enzymatic RNA replication may have been one of the processes involved in appearance life on Earth. Attempts to recreate this process a laboratory setting not successful thus far, highlighting critical need for finding prebiotic conditions that increase rate and yield. Now highly parallel assay template directed synthesis is presented relies intrinsic fluorescence 2-aminopurine modified G-quadruplex. The application examine combined influence multiple variables including pH, divalent...
Eine radikal(isch)e Lipidierung: neue Thiol-En-Lipidierung ermöglicht die einstufige Synthese von antigenen Peptiden mit Eigenverstärkungseffekt als Impfstoffkandidaten. Es wird gezeigt, dass erhaltenen Monoacyllipopeptide Monocyten aktivieren.
The clinical significance of batch-wise variability on the pharmacokinetics and potency commercial erythropoietin (EPO), prepared recombinantly as a heterogeneous mixture glycoforms, necessitates development synthetic strategies to afford homogenous EPO formulations. Herein we present previously unexplored divergent route towards 'click' neoglycoprotein analogues EPO, employing one-pot native chemical ligation (NCL) alkynylated peptides copper-catalysed azide-alkyne cycloaddition (CuAAC)...
Abstract Non‐enzymatic RNA replication may have been one of the processes involved in appearance life on Earth. Attempts to recreate this process a laboratory setting not successful thus far, highlighting critical need for finding prebiotic conditions that increase rate and yield. Now highly parallel assay template directed synthesis is presented relies intrinsic fluorescence 2‐aminopurine modified G‐quadruplex. The application examine combined influence multiple variables including pH,...
<i>S</i>-[2,3-Bis(palmitoyloxy)propyl]cysteine (Pam<sub>2</sub>Cys) is a synthetic lipid motif known to act as TLR2 agonist when incorporated into peptide vaccines. Herein, we report the synthesis of Pam<sub>2</sub>Cys-containing, propargyl-functionalised 'clickable' building blocks and their conjugation with azide-functionalised antigenic peptides using click chemistry. This method facilitates fully convergent preparation self-adjuvanting lipopeptides for use
A striking decrease in thermal stability was observed upon incorporation of triazole-linked galactosylated-lysine into an adiponectin model peptide, suggesting possible applications ‘click’ glycomimetics bioengineering.
ABSTRACT Achieving multiple cycles of RNA replication within a model protocell would be critical step towards demonstrating path from prebiotic chemistry to cellular biology. Any for early life based on an ‘RNA world’ must account strand cleavage and hydrolysis, which degrade primitive genetic information lead accumulation truncated, phosphate-terminated strands. We show here that the phosphodiester backbone is not endpoint replication. Instead, 3′ -phosphate terminated strands are able...
Abstract Die ortsspezifische (Gen‐)Mutagenese ist das wichtigste Verfahren zur Umwandlung eines Protein‐Aminosäurerestes in einen anderen. Bis vor kurzem war diese Strategie auf die zwanzig Standardaminosäuren beschränkt. ständige Weiterentwicklung der Stopp‐Codon‐Suppression und verwandter Techniken zum Einbau nichtnatürlicher Aminosäuren hat den Zugang zu nichtkanonischen erweitert, indem Spielraum des Translationsapparates vergrößert wurde. Weil genetischen Veränderungen jedoch von...
Abstract Non-enzymatic RNA self-replication is integral to the ‘RNA World’ hypothesis. Despite considerable progress in non-enzymatic template copying, true replication remains challenging due difficulty of separating strands product duplex. Here, we report a prebiotically plausible solution this problem which short ‘invader’ oligonucleotides unwind an duplex through toehold/branch migration mechanism, allowing primer extension on that was previously occupied by its complementary strand....