Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• recognition; peptide-based; Introduction Molecular recognition involving amino acids or peptides are important factors in biochemical and medicinal processes [1][2][3]. Amino acids work as biosynthetic building blocks or as signaling molecules. For example, the well-known neurotransmitters glutamate and γ

• ]. Peptides are comparatively small and can be easily synthesized in the laboratory using standard synthetic protocols [14][15]. The peptide sequence can be manipulated with precise functional groups of amino acids for selective targeting biomolecules. Peptides are large enough to contain a significant number

• which have affinity for the CB[8] cavity. These substrates easily displace 6 from the CB[8] cavity and release 6 which folds again to form a pyrene excimer, which allows for the ratiometric fluorescence monitoring of those substrates. Upon screening methyl ester derivatives of hydrophobic amino acids

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• UVRR approach from peptides to proteins as binding partners for GCPs is the UV-excited autofluorescence from aromatic amino acids observed for laser excitation wavelengths >260 nm. These excitation wavelengths are in the electronic resonance with the GCP for achieving both a signal enhancement and the

• using 275 and 266 nm laser excitation, respectively. The current challenge with UVRR spectroscopy for monitoring the recognition of supramolecular ligands to proteins is the disturbing UV-excited autofluorescence from the aromatic amino acids. This autofluorescence typically occurs in the spectral range

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• described for analytes ranging from inorganic ions over low-molecular-weight neutral and charged organic compounds, such as carboxylic acids, amino acids, and nucleotides, to larger biomolecules such as peptides and proteins [1][2][3][4][5][6][13]. All of these systems have specific areas of application

A consensus-based and readable extension of Linear Code for Reaction Rules (LiCoRR)

• Benjamin P. Kellman,
• Yujie Zhang,
• Emma Logomasini,
• Eric Meinhardt,
• Karla P. Godinez-Macias,
• Austin W. T. Chiang,
• James T. Sorrentino,
• Chenguang Liang,
• Bokan Bao,
• Yusen Zhou,
• Sachiko Akase,
• Isami Sogabe,
• Thukaa Kouka,
• Elizabeth A. Winzeler,
• Iain B. H. Wilson,
• Matthew P. Campbell,
• Sriram Neelamegham,
• Frederick J. Krambeck,
• Kiyoko F. Aoki-Kinoshita and
• Nathan E. Lewis

Beilstein J. Org. Chem. 2020, 16, 2645–2662, doi:10.3762/bjoc.16.215

• . However, “ | ” was originally designed to separate the certain and uncertain parts in a fragmented glycan, where there is a possibility of different structures (UR6). Ambiguous symbol 3 – “ # ”. Originally, “ # ” was designated to signify the starting point of glycosides that are not amino acids or lipid

• recommended preserving this symbol use since it is human and computer-readable and does not overlap with any notation in the original Linear Code. Recommendation 3 – “Number.” “ # ” was defined to combine glycans with glycosides other than amino acids and lipids (Table 3: GR1). Krambeck et al. use it to

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• sequence of 20 amino acids (–His-Gly-Val-Thr-Ser-Ala-Pro-Asp-Thr-Arg-Pro-Ala-Pro-Gly-Ser-Thr-Ala-Pro-Pro-Ala–)n, and there are five sites where O-glycosylation may occur (indicated in bold). In cancerous cells, the glycans tend to be truncated or have additional sialylation [14]. For example, in mammary

• structures, but otherwise, the end-to-end distance is very similar for both bound antigens. Ramachandran analysis The φ–ψ angles of the antigens are considered using a Ramachandran plot. Figure 4 shows a Ramachandran plot for two key amino acids, the glycosylated threonine (Thr4) and neighboring aspartate

• series and histogram for the antigen and Tn-antigen in solution (A, B) and the antibody (C, D). Plots for the antigen are in (A, C) and for the Tn-antigen in (B, D). A comparison of Ramachandran analyses for two key amino acids, Asp3 and Thr4. The first row (A–D) illustrates the φ–ψ angles for amino acid

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• at simple 1D proton spectra to study ligand binding to single amino acids or small peptides to introduce the basic principles and also briefly discuss ligand-detected NMR screening methods. Review One-dimensional 1H NMR spectra and basic principles to study ligand binding by NMR Simple one

• signals from the binding partner. Therefore, this approach is only suitable to study binding of hosts to small guest molecules like amino acids and short peptides. Both a shifting of the signals (chemical shift perturbation) and line broadening are indicative of binding. The chemical shift perturbation is

• acids was monitored by tracking the amide HN and the binding constants were obtained from the resulting binding curves [41]. The binding constants of the amino acids tested cover a ≈ 5-fold range. The differences due to the amino acid side chains were investigated by molecular modeling. Ac-Phe shows the

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

•  18b) [65]. Jiang et al. also reported a series of radical coupling reactions using different CPAs 135a–g and DPZ, with the first examples using α-bromoketones 136 and α-amino acids 137 as radical precursors (Scheme 19a) [66]. The proposed mechanism proceeds through a reductive quenching cycle to

• 139 (Scheme 19b). As previously mentioned, photoredox catalysis has been widely used for the generation of imines. The Jiang group applied this to the synthesis of substituted tetrahydroquinolines (THQs) 144 from α-amino acids 145 to give racemic products in good yields and found that the addition of

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• range of biomolecules: amino acids [8], peptides [9], glycosides [10], nucleosides/nucleotides [11], and lipids [12]. Also, protein-based nano-bio-conjugates [13] have been prepared by ball milling, retaining the native properties of the proteins after mechanochemical synthesis. Boronic acids and their

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

• Chemistry (CNC), Universität Würzburg, Theodor-Boveri-Weg, 97074 Würzburg, Germany 10.3762/bjoc.16.170 Abstract Two novel unnatural amino acids, prepared by linking a dicationic purple-coloured and fluorescent naphthalene diimide (NDI) at core position to amino acid side chains of variable length, strongly

• [9]). One of the approaches relies on amino acids conjugated with various DNA/RNA-binding chromophores, thereby yielding effective spectrometric sensing systems due to their interactions with DNA. In this approach, chromophores can be combined with peptide sequences in various ways, thus giving

• preparing novel fluorophore–amino acid (AA) conjugates. The amino acids (S)-2,3-diaminopropionic acid (ʟ-Dap) and (S)-2,6-diaminohexanoic acid (ʟ-Lys) were chosen to test the difference in the aliphatic linker lengths (Figure 1) on DNA/RNA binding. For comparison purposes, reference compound 5 with 2

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

• and resulting morphologies due to electrostatic repulsion between charged amino acids. PEP-1 can also form helical or random-coil secondary structures at a relatively low concentration. The obtained pH-sensitive self-assembly behavior of the target octapeptide is expected to contribute to the

• in mind, we synthesized an octapeptide, PEP-1, which contains two valine (Val) units and one leucine (Leu) unit as the hydrophobic residues and one glutamic acid (Glu) residue, two arginine (Arg) units, and one cysteine (Cys) substituent as polar moieties (Scheme 1). This choice of amino acids

• (Glu−) amino acids [73][74]. Mechanistic insights into the observed conformational transformation via molecular dynamics simulations are underway in our laboratory. Conclusion In summary, we synthesized a naturally occurring amphiphilic peptide fragment, PEP-1, from a β-sheet lectin protein, galectin-1

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

• attractive candidates for intracellular delivery. Already a small dipeptide 9 with two Schmuck amino acids shows a strong binding (KD = 100 nM) and clustering ability towards heparin due to the strong noncovalent interaction between GCP and sulfate anions, such as glycosaminoglycans (GAGs) in heparin [26

• more stable complexes 12 with the phosphodiesters in the DNA backbone, and thus making it possible to transfect cells with shorter peptides. In 2015, the Schmuck group reported the first example of a small peptide with only four amino acids for gene transfection [27]. The binding affinity of 13 to DNA

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• C4-exo conformation of the pyrrolidine ring. Keywords: amino acids; cis–trans isomerism; fluorine; polarity; proline; Introduction Polarity is among the key features essential for understanding the behavior of organic molecules of biological origin. In particular, there is a set of polarity-related

• issues in the chemistry of amino acids, while the latter are key actors in multiple biochemical processes. In protein translation, for example, 20 (+2) amino acids are utilized for polymerizing them into a primary structure of a protein. Most of these structures share the same key elements with the

• hydrophobic, while the introduction of a polar or an ionizable group makes it hydrophilic. Two amino acids stand out from the dualistic hydrophilic/hydrophobic classification: glycine and proline (Figure 1A) [1]. The origin of their effect onto the structure polarity is not due to the presence of additional

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• natural products ranging from small molecules, such as sugars, lipids and amino acids to huge molecules [56]. Computational results A detailed mechanistic investigation of the synthesis of oxazolidinone and five-membered cyclic carbonate derivatives by the reaction between epoxide 7f and CSI has been

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

• CXC peptide building block design (single-letter code) were the terminal amino acids are cysteine (C) and the X can be any amino acid (Scheme 1a). This allows for rapid synthesis of various new building bocks by standard Fmoc based SPPS using Trt protecting groups for cysteine, which are subsequently

• cleaved (see Supporting Information File 1 for details). It also enables easy incorporation of nonnatural amino acids if desired [21]. We prepared a DCL by dissolving CFC, CEC, CSC and CAC (C for cysteine, F for phenylalanine, E for glutamic acid, S for serine, A for alanine) in an equimolar ratio in a

Azidophosphonium salt-directed chemoselective synthesis of (E)/(Z)-cinnamyl-1H-triazoles and regiospecific access to bromomethylcoumarins from Morita–Baylis–Hillman adducts

• Soundararajan Karthikeyan,
• Radha Krishnan Shobana,
• Kamarajapurathu Raju Subimol,
• J. Helen Ratna Monica and
• Ayyanoth Karthik Krishna Kumar

Beilstein J. Org. Chem. 2020, 16, 1579–1587, doi:10.3762/bjoc.16.130

• chemists. Accordingly, MBH adducts have been explored as strategic intermediates for the synthesis of interesting molecules, such as carbamates of unsaturated β-amino acids [1], β-phenylsylfenyl-α-cyanohydrocinnamaldhydes [2], 2-alkylcarbonyl-1-indanols [3], dihydropyrazoles [4], tetrahydroacridines [5], γ

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• and abundant source of biomass-derived molecules. Decarboxylative transformations of carboxylic acids into value-added chemical products (such as biofuels) are a key objective in organic synthesis [25]. In 2014, Wallentin and co-workers reported a type of decarboxylation reaction of α-amino acids, α

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• reactions [8]. Azomethine ylides can be formed by several photochemical or thermal catalytic methods [5][6][7], including photodecarboxylation of phthalimide derivatives of α-amino acids such as N-phthaloylglycine (1) [9][10]. Phthalimide is a versatile chromophore that has been used in the synthesis of

Synthesis of pyrrolidinedione-fused hexahydropyrrolo[2,1-a]isoquinolines via three-component [3 + 2] cycloaddition followed by one-pot N-allylation and intramolecular Heck reactions

• Xiaoming Ma,
• Suzhi Meng,
• Xiaofeng Zhang,
• Qiang Zhang,
• Shenghu Yan,
• Yue Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2020, 16, 1225–1233, doi:10.3762/bjoc.16.106

• Two kinds of [3 + 2] cycloaddition intermediates generated from the three-component reactions of 2-bromobenzaldehydes and maleimides with amino esters or amino acids were used for a one-pot N-allylation and intramolecular Heck reactions to form pyrrolidinedione-fused hexahydropyrrolo[2,1-a

• stabilized azomethine ylides I-a generated from the condensation of aldehydes and amino esters for making pyrrolidines II-a have been well-reported [23][24][25][26], while the [3 + 2] cycloaddition of the less stable azomethine ylides I-b generated from the reaction of aldehydes and amino acids for

• due to the low yield at the N-allylation step. Same result happened to 9o in which hindered iBu blocked the N-allylation. We next employed intermediated 6 prepared from the decarboxylative [3+2] cycloaddition of amino acids for one-pot N-allylation and intramolecular Heck reactions under the same

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• . Other organic dyes, including several acridinium salts, have been successfully applied in organophotocatalytic decarboxylation protocols. For example, rhodamine 6G (OD14, E(PC+*/PC) ≈ 1.2 V) [42] was used for the photocatalytic decarboxylative azidation of cyclic amino acids and rose bengal (OD15) [43

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• complexes 4. Treatment of 4 with CO in a MeOH/NCMe mixture promoted the methoxycarbonylation of the palladated carbon and the release of the corresponding ortho-functionalized 1,3-diaminotruxillic bis-amino esters 5 as single isomers. Keywords: amino acids; C–H activation; Kaede protein; oxazolones

• ortho-position of the 2,4-aryl rings in the resulting bis-amino acids can be functionalized [30]. Substrates of the (Z)-4-arylidene-2((E)-styryl)-5(4H)-oxazolone type, shown in Figure 2b, are interesting starting materials for the synthesis of new 1,3-diaminotruxillic derivatives. These azlactones are

• findings were also confirmed by analysis of the 13C NMR spectra. Conclusion The synthesis of cyclobutane 1,3-diaminotruxillic bis-amino acids has been achieved with full stereoselectivity (ε-isomer) starting from polyfunctional oxazolones 2 derived from the chromophore of the Kaede protein in three steps

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

• , geometry, conformation, reactivity, and moreover the bioavailability of the analogue [1]. Fluorinated amino acids (FAAs) have considerable industrial and pharmaceutical potential [2]. Also, they have played an important role as enzyme inhibitors as well as therapeutic agents [3][4]. Moreover, they modulate

• membrane permeability and reactivity [11][12][13][14]. The effect of peptide structure and stability has been found to depend on the position and number of fluorine atoms within the amino acid chains [15][16][17]. Incorporation of fluorinated aromatic amino acids into proteins can increase their shelf life

Fabclavine diversity in Xenorhabdus bacteria

• Sebastian L. Wenski,
• Harun Cimen,
• Natalie Berghaus,
• Sebastian W. Fuchs,
• Selcuk Hazir and
• Helge B. Bode

Beilstein J. Org. Chem. 2020, 16, 956–965, doi:10.3762/bjoc.16.84

• formula [28]. The general structure of the fabclavines is highly conserved and differs only in the specified moieties as shown in Table 1. The NRPS part of the full-length fabclavines harbors six amino acids, whereby the second position (R1) varies between phenylalanine (Phe), histidine (His), and alanine

• of two A-domains A2 and A6 in the NRPSs FclI and FclJ (Figure 1) [22]. Surprisingly, the key residues of these domains are highly conserved or identical, even between strains that differ in the incorporated amino acids (Table S6, Supporting Information File 1). This indicates the involvement of

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• using 4 mol % of tetra-n-butylammonium fluoride (TBAF) as an activator of TMSCN (conditions B). Following this second protocol, the primary α-aminonitriles were rapidly prepared in relevant yields (up to 87%) and converted to the corresponding α-amino acids by hydrolysis of the nitrile (Scheme 57

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• cell surfaces for future investigations by combined preparative mass spectroscopy and scanning tunneling microscopy (STM) using soft-landing electrospray beam deposition (ES-IBD), on metal surfaces. Keywords: amino acids; asparagine; carbohydrates; glycopeptides; peptidomimetics; Introduction

• example, in anti-HIV therapy, MUC1-based antitumor vaccines, or as antibiotics [12][13][14]. Especially glycans bearing noncanonical amino acids, which can only be introduced into a peptide by organic synthesis, are suitable for cancer therapy since they show better resistance to enzymatic degradation in

• comparison with naturally occurring amino acids [14]. Thus, there is still a great effort in finding new potential drugs derived from glycopeptides [4][15]. By using preparative mass spectrometry (pMS) combined with STM on submolecular-resolution peptides and carbohydrates can be investigated regarding their