Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• University, Sakyo, Kyoto 606-8501, Japan 10.3762/bjoc.20.39 Abstract The adenylation (A) domain is essential for non-ribosomal peptide synthetases (NRPSs), which synthesize various peptide-based natural products, including virulence factors, such as siderophores and genotoxins. Hence, the inhibition of A

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• permeability [1][2][3]. Hence, peptide-based drugs became of high interest because of their high selectivity combined with low toxicity. Cross-linking of side chain residues results in constrained conformations and can be used to stabilise α-helical secondary structures. This technique is called peptide

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• bonding moieties are either urea-based or peptide-based (i.e., phenylalanine) units, the dodecyl chains act as hydrophobic shields to induce the amphiphilic assembly in water and prevent the surrounding water from interfering with the hydrogen bonds in the interior [29]. Attaching a hydrophilic PEO chain

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• 31n, regarded as a potentially viable peptide-based biosensor. Manganese-catalyzed inter- and intramolecular C–H alkenylations Manganese(I)-catalyzed C–H alkenylation of 2-phenylpyridines or N-pyridinylindoles with alkynes is characterized by proximity-induced C–H activation through chelation

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• mixture was subsequently purified by size exclusion chromatography to yield 85% of the oligosulfated monomer II. Characterization of the supramolecular polymers of I and II The self-assembly behavior of the peptide-based materials can be readily investigated using CD spectroscopy. The supramolecular

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• Debabrata Maity Department of Chemistry, New York University, New York, NY 10003, USA 10.3762/bjoc.16.247 Abstract To understand the molecular interactions, present in living organisms and their environments, chemists are trying to create novel chemical tools. In this regard, peptide-based

• fluorescence techniques have attracted immense interest. Synthetic peptide-based fluorescent probes are advantageous over protein-based sensors, since they are synthetically accessible, more stable, and can be easily modified in a site-specific manner for selective biological applications. Peptide receptors

• labeled with environmentally sensitive/FRET fluorophores have allowed direct detection/monitoring of biomolecules in aqueous media and in live cells. In this review, key peptide-based approaches for different biological applications are presented. Keywords: fluorescent probe; fluorophores; molecular

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• peptide chain and DNA/RNA interacting aromatic moiety, for instance peptide-based DNA/RNA-intercalators [1][2], as well as many DNA/RNA groove binding small molecules [3][4]. Inspired by these natural examples, the development of novel DNA/RNA targeting synthetic molecules has been in scientific focus for

• access to large libraries of close analogues. Further, in such peptide-based chromophore systems, a multitude of different chromophores/fluorophores [10] could allow fine tuning of spectroscopic responses to various DNA/RNA sequences. With this concept in mind, Piantanida and co-workers recently

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• Goutam Ghosh Gustavo Fernandez Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Correnstraße 40, 48149 Münster, Germany 10.3762/bjoc.16.168 Abstract Peptide-based biopolymers represent highly promising biocompatible materials with multiple applications, such as tailored

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• with the HC CAPA. To quantify the impact of the HC CAPA on the detection of the cytosolic delivery, the newly introduced peptide-based COC 23 was evaluated for the transport of a model protein with the new analytical improvements. With a CP50 value of 7.3 ± 0.5 μM with the mitochondrial mask, complex

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• , which is in agreement with the apparently weaker interaction in D2O [25]. Conclusion In summary, we demonstrated that artificial peptide receptors can emerge from a peptide-based DCL under competitive conditions in water. In agreement with our previous works on carbohydrate recognition, this supports

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• . Incorporation of fluorinated aromatic amino acids into proteins increases their catabolic stability especially in therapeutic proteins and peptide-based vaccines. This review seeks to summarize the different synthetic approaches in the literature to prepare ᴅ- or ʟ-fluorinated phenylalanines and their

• , especially in therapeutic proteins and peptide-based vaccines [18]. Enhanced catabolic stability [6] can arise from the role of particular aromatic amino acids in membrane–protein interactions [19]. Furthermore, fluorinated aromatic amino acids can alter enzymatic activity as a result of enhanced protein

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• slides [46][47], steroids [48][49], calixpyrroles [50][51], calixarenes [52][53], and other scaffolds [54][55][56]. In particular, peptide based transmembrane anion transporters have attracted great interest. For example, Ghadiri [38], Ranganathan [39], and Granja [40] have independently reported

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• of the important cyclic peptide Chap-31 may encourage the preparation of cyclic peptide based HDAC inhibitors. The developed methodology may hence complement the existing literature on the preparation of such class of compounds and may find applications. Experimental General procedure for cross

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• gallolyticus subsp. gallolyticus [18], Streptococcus pneumoniae [19], and Lactobacillus plantarum. These circuitries are usually centered on a peptide signal, rather than a small molecule, and are fruitful ground for the development of peptide-based therapeutics. S. pneumoniae is an opportunistic human

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• may lead to novel insights about the innate immune system and to new peptide-based anticancer chemotherapies. Conclusion Current cancer treatments are associated with numerous harmful side effects, which warrants the discovery of novel forms of treatment. ACPs have been proposed as novel anticancer

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• this study when positioned N-terminal to the cleavage site. These results provide valuable information for the application of fluorinated amino acids in the design of proteolytically stable peptide-based pharmaceuticals. Keywords: fluorinated amino acids; hexafluoroleucine; peptide drugs; protease

• stability; trifluoroisoleucine; Introduction Peptide-based drugs are promising pharmaceuticals since they offer several advantages including high selectivity, specificity, and efficacy for recognizing and binding to their targets [1][2][3][4][5][6]. However, their application as drugs is often limited due

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• development of peptide-based contrast agents for 19F imaging [22]. In polypeptides, the incorporation of fluorine can significantly alter the properties of the native molecule. The hydrophobicity [23][24], conformational equilibria [25], and the thermodynamic [26][27][28][29] and kinetic [30][31] folding

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• of the relative positioning of the reaction counterparts. This peptide-based templating was extended to the synthesis of a small library of disaccharides. Non-symmetrical and other tethers Non-symmetrical templates have also been developed with a general idea of achieving differentially cleavable

• glycosidation. Molecular clamping with the phthaloyl linker in the synthesis of α-cyclodextrin. m-Xylylene as a rigid tether for intramolecular glycosylation. Oligosaccharide synthesis using rigid xylylene linkers. Stereo- and regiochemical outcome of peptide-based linkers. Positioning effect of donor and

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• strands by creating heat gradients in pores that act as a thermal trap [38]. The thermal traps selectively retain longer DNA sequences, thereby effectively overcoming the inherent advantage of the replication of short sequences. 3.2 Dynamics of self-replicators Ashkenasy recently reported a peptide based

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• the first (iso)peptide-based metabolic pathways one finds iron–sulfur clusters (pyrite) [20] and polyphosphates [27]. Obviously, selected peptides would be part of the first prebiotic building blocks and compounds, exhibiting a range of promiscuous catalytic activities. This includes hydrolytic self

• , appeared after an (iso)peptide-based metabolism was commonplace. Cofactors such as pterins and riboflavin are ubiquitously present in living organisms. Precursors of these essential compounds may have been synthesised by a thioester swinging-arm pathway and phosphorylated by polyphosphate. Remarkably, in

• this intelligent way, but unfolded more slowly. The actual emergence of the genetic code required a succession of small steps involving progressive improvement of peptide-based metabolism. As expected from a stepwise development, this process created a fair number of anecdotal features that were

A direct method for the N-tetraalkylation of azamacrocycles

• Andrew J. Counsell,
• Angus T. Jones,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2016, 12, 2457–2461, doi:10.3762/bjoc.12.239

• peptide-based disulfide macrocycles in a dynamic combinatorial library [49]. They observed different product distributions when reaction mixtures were shaken than when stirred, concluding that “mechanical forces can ... determine the outcome of a covalent synthesis” and that the ‘mechanosensitivity’ of

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• oxidation of cyclic ketones 101 bearing amido, ureido, or sulfonamido functional groups to lactones 102 and 103 was carried out using the peptide-based catalyst 104. Hydrogen-bonding interactions are responsible for both types of selectivity. Notably, a reversal of the typically seen selectivity was

Synthesis and evaluation of the biostability and cell compatibility of novel conjugates of nucleobase, peptidic epitope, and saccharide

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum,
• Khalid Omar Al Footy,
• Khadija Omar Badahdah and
• Bing Xu

Beilstein J. Org. Chem. 2015, 11, 1352–1359, doi:10.3762/bjoc.11.145

• ). Biostability The existence of proteolytic enzymes [39] in organism limits the applications of peptide-based biomaterials [40] in vivo. To evaluate the biostability of the conjugates 1–8, we incubated them with proteinase K (a powerful protease) in HEPES buffer at 37 °C for 24 h. As shown in Figure 3A

Impact of multivalent charge presentation on peptide–nanoparticle aggregation

• Daniel Schöne,
• Boris Schade,
• Christoph Böttcher and
• Beate Koksch

Beilstein J. Org. Chem. 2015, 11, 792–803, doi:10.3762/bjoc.11.89

• ] interactions have been explored. In particular, peptide-based assemblies afford numerous advantages such as the modification of nanostructures by mutations of the primary sequence of peptides which may lead to the formation of various hierarchical morphologies [23][24][25]. The strategies for the assembly of

• assembly [9]. Peptide-based nanoparticle aggregation was demonstrated first by Woolfson and coworkers by means of coiled-coil peptides that were immobilized on the nanoparticle surface [26]. Reversibility of the assembly formation, a key feature of a switchable system, has thus far been explored only for a

Potential of acylated peptides to target the influenza A virus

• Daniel Lauster,
• Damian Pawolski,
• Julian Storm,
• Kai Ludwig,
• Rudolf Volkmer,
• Henry Memczak,
• Andreas Herrmann and
• Sumati Bhatia

Beilstein J. Org. Chem. 2015, 11, 589–595, doi:10.3762/bjoc.11.65

• mediated by a multivalent interaction between HA binding pockets and cell surface receptors as a monovalent interaction is too weak for stable binding [10][11]. Peptide-based self-assembled nanostructures can be used as the simplest platform for the multivalent display of ligands, although this approach

• has not been explored much in the context of virus inhibition. There are only a few reports on using peptide based self-assembly for influenza virus inhibition [12][13][14]. The entry blocker (EB) which is a peptide fragment derived from the fibroblast growth factor signal sequence 4 (FGF) has a