Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• compounds. Furthermore, from this perspective, the formed probe–protein covalent conjugate shares many features with naturally occurring protein post-translational modifications (PTMs) offering productive exchange of the techniques and experimental setups used in both fields (Figure 2B) [33][34]. The second

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• -translational modifications, including glycosylation, in which a carbohydrate chain is directly attached to a specific amino acid to generate glycoproteins and proteoglycans [27]. Based on the amino acid involved in the link with the carbohydrates chain, it is possible to classify different types of

• of chemical processes [20][21], transporting and storing molecules [22], transducing and integrating information [23] providing structural and mechanical support [24], and generating movement [25], among other functions [26]. To fold and carry out their function properly, proteins often need post

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• , including one super-cluster containing two co-localized operons from Clostridium cellulovorans 743B, that encode for two new peptides named clostrisin and cellulosin. Each operon was heterologously expressed in Escherichia coli. Molecular weights associated with the expected post-translational modifications

• activity of nisin, a lanthipeptide produced by certain strains of Lactococcus lactis, is dependent on thioether-ring formation [14]. Additional post-translational modifications contributing to their distinct biological activities were identified [15][16]. Intermolecular disulfide bridges were proved to

• several precursors, forming superclusters. The RiPPMiner platform [5] was used to predict in silico post-translational modifications of the mature lanthipeptides. Based on these predictions, several clusters did not contain precursor peptides with a predicted lanthipeptide heterocycle formation and were

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• encoded in the same BGC as the precursor peptide install post-translational modifications in the core peptide. Finally, a protease releases the modified core peptide, creating the mature natural product [2]. The transfer of a methyl group is a common post-translational modification in RiPP biosynthesis

• . However, using SAM supply or regeneration systems may be useful if the peptide substrate cannot be synthesised ribosomally, e.g., if it contains non-proteinogenic amino acids that cannot be produced by post-translational modifications of RiPP pathways. SAM supply or SAM regeneration systems typically

• peptide structures. The remaining challenges include combining various post-translational modifications and developing a medium to high throughput screening approach to subject interesting peptide drug candidates to various MTs and perform SAR studies (structure–activity relationship). Overall, RiPP MTs

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• -translational modifications by specific tailoring enzymes [5][6]. This precursor peptide substrate can be subdivided into multiple segments including 1) an N-terminal leader or recognition sequence used for binding by the tailoring enzymes and 2) a core peptide that is targeted for modification by the

• prevalent in plants [4]. Like all known plant peptides, burpitides fall under the ribosomally synthesized and post-translationally modified peptides (RiPPs) superclass of natural products (Figure 1). The typical pathway for a RiPP starts with a precursor peptide made by the ribosome that undergoes post

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• , as an archetypal example of melon lectins. For this, we needed to express the lectin recombinantly. As it is a secreted plant protein, we elected to express it in mammalian cell lines, to maximize the chances of a functional protein, because of post-translational modifications that would be lacking

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• mammalian COXs revealed that COX-1 and COX-2 are both glycosylated by post-translational modifications [46][47][48][49][50][51]. These enzymes form homodimers, and the overall structures of COX-1 and COX-2 superimpose well, with root mean square values of ≈0.9 Å. Each COX monomer contains three domains

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• methionine aminopeptidase type-2 (MetAP-2) enzyme [129]. MetAP-2 is involved in cell proliferation, translation and post-translational modifications of nascent polypeptides and is therefore essential for cell viability [130][131]. Additionally, fumagillin is also known to be overproduced upon caspofungin

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• structural informatics tools. Keywords: data analysis; glycan binding; glycan microarray; glycomics; informatics; Introduction Glycans represent a major type of biomolecule in all living things, along with DNA, RNA, lipids and proteins [1]. In mammals, glycans commonly occur as post-translational

• modifications of proteins (glycoproteins), but they are also linked to lipids (glycolipids) and occur as free molecules. Such glycomolecules have vital roles in a wide range of physiological functions and also participate in many pathologic conditions [2]. Some classic examples of important glycans include the

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• Carl A. Fogarty Aoife M. Harbison Amy R. Dugdale Elisa Fadda Department of Chemistry and Hamilton Institute, Maynooth University, Maynooth, Kildare, Ireland 10.3762/bjoc.16.171 Abstract The N-glycosylation is one of the most abundant and diverse post-translational modifications of proteins

A stereoselective and flexible synthesis to access both enantiomers of N-acetylgalactosamine and peracetylated N-acetylidosamine

• Bettina Riedl and
• Walther Schmid

Beilstein J. Org. Chem. 2018, 14, 856–860, doi:10.3762/bjoc.14.71

• , glycoproteins serve as ligands for specific extracellular recognition processes toward, e.g., enzymes, lectins or antibodies [2]. In O-linked glycoproteins, also known as mucins, GalNAc becomes covalently α-linked to serine or threonine during post-translational modifications [3][4][5]. This glycoconjugate

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

• structural biology community, with more than 85% of the protein structures deposited in the Protein Data Bank being expressed in Escherichia coli. However, many proteins require post-translational modifications for correct biological activity and it is estimated that more than 50% of all human proteins are

• the surface of the protein. For a given glycoprotein, there may exist considerable variations of N-linked glycan chains from protein to protein. Such a heterogeneous macromolecular mix is not suitable for crystal formation. Large post-translational modifications also have the effect of increasing

Posttranslational isoprenylation of tryptophan in bacteria

• Masahiro Okada,
• Tomotoshi Sugita and
• Ikuro Abe

Beilstein J. Org. Chem. 2017, 13, 338–346, doi:10.3762/bjoc.13.37

• with other biosynthetic studies on prenylated cyanobactins, KgpF functions at the end of the biosynthesis, and recognizes two tryptophan residues in the precursor cyclic peptide to form kawaguchipeptin A. In contrast to typical post-translational modifications, a specific amino acid motif adjacent to

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• database which has non-redundant protein sequences which are manually annotated to contain descriptions such as functional information of protein sequences and post-translational modifications [84]. PDB and Swiss-Prot are both general purpose biological databases. There are other databases that contain

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• characteristics, outstanding stability, regular fibrous architecture and high synthetic accessibility with numerous chemoselective ligation and modification methods [24][25][26]. Also, various post-translational modifications, like phosphorylation or glycosylation have been studied as aggregation triggers [27][28

• understanding of the process. Conclusion Post-translational modifications like phosphorylation have become the most promising approach to examine and control the pathway of amyloid fibrillization. For a better understanding of the challenges of phosphorylation in this context, we designed a model peptide which

From supramolecular chemistry to the nucleosome: studies in biomolecular recognition

• Marcey L. Waters

Beilstein J. Org. Chem. 2016, 12, 1863–1869, doi:10.3762/bjoc.12.175

• ][23], and Alextide – for which folding can be turned on or off with post-translational modifications (after Alex Riemen) [32]. Biological significance and a shift in focus While studying aromatic interactions in β-hairpins in the early 2000’s, an important biological discovery was made: a crystal

• -translational modifications such as trimethyllysine are antibodies, but antibodies have significant limitations in this context, as they are too sequence specific. Thus, we aimed to develop synthetic receptors that would mimic the binding pockets of proteins to recognize trimethyllysine, but not the surrounding

• highly amenable to structure–function studies, since only a new monomer must be synthesized, rather than an entirely new receptor. With my interest in trimethyllysine provided a significant problem in which DCC seemed to be a promising solution. It turns out that the main tool for sensing protein post

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• biologically active peptide natural product (Figure 1 and Figure 2). A huge variety of RiPP post-translational modifications have been identified [5][14]; some are specific to certain classes of RiPP while others occur across the entire RiPP spectrum. These modifications can range from leader peptide

• oxazolones and pyrazinediones [150][153][154], which are found alongside thioamides in these molecules (Figure 11). These post-translational modifications are critical for copper binding but the mechanisms of these heterocyclisation steps have not yet been determined for any pathway, despite the

• and characterisation of RiPP post-translational modifications in recent years [5][14]. Much of this has been led by genomics, which has informed both the study of established molecules whose biosynthetic origins were previously unknown (e.g., thiostrepton [72]) and the discovery of new pathways via

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• “oncogenic Hsp90”, both with regards to its onco-client protein content and the nature of its distinct post-translational modifications. This is in contrast to immunoprecipitation of Hsp90, which we have shown to identify and isolate both “oncogenic Hsp90” (i.e., PU-H71-binding) and “housekeeping Hsp90” (i.e

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• scaffolds by investigating their structural and functional impact. Currently, oligosaccharides are known to have functions in a broad variety of cell–cell interactions related to invading bacteria, viruses and cancer cells [1][2][3][4] and to play central roles in post-translational modifications of