Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• study the mechanism of action of antimicrobial peptides that kill bacteria through binding to these polyprenyls [21][28][29][30][31][32][33][34]. Lipid II has been of particular interest, and during our synthesis of multiple different lipid II analogues, we have developed several optimizations, which we

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• activity have revealed the presence of antimicrobial peptides [5], defensive alkaloids [6], and defensive long chain alcohol acetates [7]. Historically, in China, numerous records documented the utilization of animals like arthropods for medicinal purposes. Millipedes hereby represent a traditional Chinese

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• alignments with known genes and domains using algorithms like BLAST (Figure 4) [42]. BLAST detects similar sequences to a given query sequence [42]. The first version of the tool BAGEL utilized BLAST analysis, among others, to identify putative BGCs of bacteriocins (= antimicrobial peptides and proteins) [43

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• increasingly prominent in 19F NMR studies owing to their improved spectral properties. Among the first perfluorinated amino acids to be reported was perfluoro-tert-butylhomoserine (8), which was synthesized by Marsh and co-workers and incorporated into a variety of antimicrobial peptides, including MSI-78, for

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• identified as a major mechanism contributing to antimicrobial resistance of Gram-negative pathogenic bacteria. Inhibition of the corresponding enzymatic steps, specifically the transfer of 4-amino-4-deoxy-ʟ-arabinose, would thus restore the activity of cationic antimicrobial peptides and several

• cationic antimicrobial peptides with the negatively charged phosphate and carboxylate groups in LPS domains. Suitable inhibitors intercepting the attachment of Ara4N units to the lipid A and inner core region might restore sensitivity towards the cationic antimicrobial drugs as a novel approach to combat

Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety

• Iteng Ng-Choi,
• Àngel Oliveras,
• Lidia Feliu and
• Marta Planas

Beilstein J. Org. Chem. 2019, 15, 761–768, doi:10.3762/bjoc.15.72

• File 410: Experimental, synthesis, and characterization of all the compounds. Acknowledgements Parts of this manuscript are adapted from the Ph. D. dissertation of Iteng Ng-Choi, Universitat de Girona, 2015: Solid-Phase Synthesis of 5-Arylhistidine-Containing Peptides: from Linear Antimicrobial

• Peptides to Cyclic Peptides Derived from Arylomycins and Aciculitins. The authors acknowledge the Serveis Tècnics de Recerca of the University of Girona for the MS analysis. This work was supported by the Ministerio de Economía y Competitividad (MINECO) [grant numbers AGL2009-13255-C02-02/AGR, AGL2012

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

• and to avoid toxicity towards normal host cells. Antimicrobial peptides (AMPs) are produced by the innate immune system of virtually every organism on Earth. These agents represent promising anticancer candidates since, in addition to their activity vs bacteria [1], viruses, parasites [2][3][4][5][6

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• integrity and antigen presentation, decreases susceptibility to antimicrobial peptides and enhances pathogenicity [25]. In some LPS, the lipid A phosphates are post-translationally modified by substitution with the compounds that reduce the net negative charge of LPS, such as phosphoethanolamine in E. coli

• to the phosphate groups of lipid A alters the TLR4-mediated host immunity and accounts for the modulation of the pro-inflammatory signaling. Additionally, this modification is associated with an amplified bacterial virulence since it confers resistance to the endogenous cationic antimicrobial

• peptides (CAMPs) and antibiotics [25][32][33][34]. Activation of the innate immune response by lipid A/LPS requires a consecutive interaction of lipid A with lipopolysaccharide-binding protein (LPB) [35], glycosylphosphatidylinositol-anchored surface protein CD14 (a differentiation antigen of monocytes

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

• proteolytic degradation in particular. Meng and Kumar reported that the incorporation of 5,5,5,5’,5’,5’-hexafluoroleucine (HfLeu) into the antimicrobial peptides magainin 2 amide and buforin enhanced their resistance towards proteolytic degradation by trypsin [23]. They also introduced HfLeu into the glucagon

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

• antimicrobial peptides (AMPs) that have important roles in the mammalian immune system [143], including in humans [144], and these AMPs often exist as a cocktail of compounds. Many of these are unmodified linear peptides, such as the human peptide cathelicidin LL-37 [145], or are cyclised by disulphide bonds

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• via horizontal gene transfer. Cystobactamids: The cystobactamids were recently isolated from a Cystobacter sp. and represent a novel class of NRPS-derived antimicrobial peptides [113]. Cystobactamids 919-1 and 919-2 (Figure 5) display an unusual aromatic scaffold composed of p-nitrobenzoic acid and

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• cholesterol (oxysterol) metabolites contributes to the prognosis of major chronic diseases. Cholesterol is completely absent in prokaryotic organisms [1][2][3]. Cholesterol gives eukaryotic membranes sufficient mechanical stiffness against cationic selective antimicrobials (CSAs) such as antimicrobial

• peptides (AMPs) [4] and ceragenins I (Figure 1) [5]. These CSAs selectively bind to the over expressed negatively charged peripheral phospholipids on the internal bacterial cell membranes. Following membrane association, deformation occurs causing bilayer destabilization and cell lysis [6]. According to

Multivalent display of the antimicrobial peptides BP100 and BP143

• Imma Güell,
• Rafael Ferre,
• Kasper K. Sørensen,
• Esther Badosa,
• Iteng Ng-Choi,
• Emilio Montesinos,
• Eduard Bardají,
• Lidia Feliu,
• Knud J. Jensen and
• Marta Planas

Beilstein J. Org. Chem. 2012, 8, 2106–2117, doi:10.3762/bjoc.8.237

• antimicrobial peptides. Herein, we describe the design and synthesis of chimeric structures containing two or four copies of the antimicrobial peptides KKLFKKILKYL-NH2 (BP100) and KKLfKKILKYL-NH2 (BP143) attached to the carbohydrate template cyclodithioerythritol (cDTE) or α-D-galactopyranoside (Galp). The

• - to 8-fold more active than the monomeric peptide against the phytopathogenic bacteria. These results suggest that preassembling antimicrobial peptides to multimeric structures is not always associated with a significant improvement of the activity. In contrast, the carbopeptides synthesized were

• ; Introduction The emergence of antibiotic resistance is a major problem in human health as well as in agronomy and there is a considerable current interest in developing novel antimicrobial compounds [1][2]. In recent years, a growing number of studies have shown that antimicrobial peptides constitute a

Modulating the activity of short arginine-tryptophan containing antibacterial peptides with N-terminal metallocenoyl groups

• H. Bauke Albada,
• Alina-Iulia Chiriac,
• Michaela Wenzel,
• Maya Penkova,
• Julia E. Bandow,
• Hans-Georg Sahl and
• Nils Metzler-Nolte

Beilstein J. Org. Chem. 2012, 8, 1753–1764, doi:10.3762/bjoc.8.200

• of ~90 µM, indicating a potentially interesting therapeutic window. Both the killing kinetics and growth inhibition studies presented in this work point to a membrane-based mode of action for these two peptides, each having different kinetic parameters. Keywords: antimicrobial peptides; arginine

• and antimicrobial peptides with bacteria-specific membrane targeting modes of action (MOA) to which resistance cannot easily develop has led to high expectations in the treatment of bacterial infections [2][3][4]. Whereas host-defense peptides are found in many multicellular organisms as part of their

• innate immune system, the name “antimicrobial peptides” (abbreviated as AMPs) defines a larger group of peptides that also encompasses synthetic peptides, and peptidomimetics, for example. Among these, synthetic peptide-based antimicrobial agents are especially interesting because isolation and/or

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• biological activity of antimicrobial peptides. This information was used to design a novel antimicrobial peptide sequence by using an intrinsically inactive membrane-associated peptide derived from the HIV glycoprotein, gp41, as a starting scaffold. This peptide corresponds to the tryptophan-rich membrane

• extremely hemolytic. This work demonstrates a novel approach for the design of unexplored antimicrobial peptide sequences but it also reveals that the biological and cytotoxic activities of these polypeptides depend on a number of interrelated factors. Keywords: antimicrobial peptides; cytotoxic peptides

• ; NMR solution structure; membrane interactions; peptides structure–function relationship; Introduction Antimicrobial peptides (AMPs) continue to attract significant attention as potential alternatives to conventional antibiotics. A large number of AMP sequences have been reported in the literature

Similarity analysis, synthesis, and bioassay of antibacterial cyclic peptidomimetics

• Workalemahu M. Berhanu,
• Mohamed A. Ibrahim,
• Girinath G. Pillai,
• Alexander A. Oliferenko,
• Levan Khelashvili,
• Farukh Jabeen,
• Bushra Mirza,
• Farzana Latif Ansari,
• Ihsan ul-Haq,
• Said A. El-Feky and
• Alan R. Katritzky

Beilstein J. Org. Chem. 2012, 8, 1146–1160, doi:10.3762/bjoc.8.128

• example in the form of nasal or throat sprays but, at least one anionic peptide, daptomycin, is administered intravenously. The abundance of natural and synthetic antimicrobial peptides and peptidomimetics of varying structure and activity reported raises the question of how their similarity or

Antibiotic and cytotoxic peptides

• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1144–1145, doi:10.3762/bjoc.8.127

• . Some antibiotic peptides are an essential part of innate immunity, which has evolved in most organisms to combat microbial challenge. In addition, antimicrobial peptides sometimes also display cytotoxicity against mammalian cells. There are several good reasons for a Thematic Series in the Beilstein