Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• phylogenetic tree, we used the MUSCLE algorithm (gap open, −2.9; gap extend, 0; hydrophobicity multiplier, 1.2; max. iterations, 8; clustering method, upgmb) implemented in MEGA7 [89] to compute an amino acid alignment. Based on the MUSCLE alignment, the tree was constructed with MEGA7 using a Maximum

• amino acid substitutions per site. The alpha-domain of maize TPS4 [62] was chosen as an outgroup. TPS proteins from different Ascomycota are highlighted according to their different lifestyle: endophytic (purple), pathogenic (orange) and saprophytic (green). Fungal endophytes identified from leaves of

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• phosphono-PNAs retained the stability against nucleases. In another study, conjugation with glutamine phosphonate or lysine bis-phosphonate amino acid derivatives introduced up to twelve negative charges (phosphonate moieties) into PNAs [91]. The negative charges allowed cationic lipid-mediated delivery of

• conjugate approach involved the conjugation of PNA to (ᴅ)-insulin-like growth factor 1 peptide (IGF1) that enabled the delivery to cells expressing the IGF1 receptor [166]. Later developments adopted CPPs derived from natural proteins (Figure 12A), such as penetratin (16-amino acid peptide from the third

• helix of the Antennapedia homeodomain) [167], Tat (14-amino acid peptide from HIV-1 TAT protein) [168], and transportan (chimeric 27-amino acid peptide derived from galanin and mastoparan) [169]. Corey and co-workers were the first to demonstrate that conjugation of an 11-mer PNA to penetratin peptide

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• the synthesis of (–)-AG-041R, a gastrin/cholecyctokinin-B receptor antagonist. In addition, amino ester 55 was transformed into the fully unprotected amino acid 56 under basic conditions in MeOH, and after that, further treatment with of MsCl and NaHCO3 in MeCN at 80 °C led to spiro-β-lactam

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• columns. Initially, fluorenylmethyloxycarbonyl (Fmoc) group removal from the Rink linker was achieved by applying 20% piperidine in DMF (2 × 30 min). Preactivation of Fmoc amino acid (4 equiv) prior each coupling was performed with 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide

• hexafluorophosphate (HATU, 4 equiv) and N,N-diisopropylethylamine (DIPEA, 6 equiv) in DMF. Then, the activated mixture was added to the resin swollen in DMF, and manual stirring was applied approximately every 15 min over a total reaction time of 2 h. The first amino acid was installed via double coupling. Fmoc

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• plausible mechanism shown in Scheme 14 explains the formation of azomethine ylide B by condensation of isatin with amino acid followed by release of a molecule of CO2 via A. The imine B undergoes 1,3-dipolar cycloaddition with the dipolarophiles 39. The cyclization yields the desired product 40 of the three

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• synthesis of unnatural α-amino acids 129 and precise alkylation modification of peptides in the later stage (Scheme 45). Even in the presence of other amino acid residues, this protocol has excellent regio- and chemoselectivity, providing a sequence of novel corresponding dipeptides with good yield. The

• acylation product 123 initiated by an EDA complex. Mechanism of the synthesis of acylation product 123. Synthesis of trifluoromethylation product 126 initiated by an EDA complex. Synthesis of unnatural α-amino acid 129 initiated by an EDA complex. Synthesis of thioether derivative 132 initiated by an EDA

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• the main characteristics of C60 stimulated a great interest in the application of fullerenes in medical chemistry. Of the fullerene-based biologically significant molecules, amino acid derivatives are of particular interest. In fact, Prato and co-workers synthesized and characterized the first peptide

• dimethoxymethanofullerene 7. Synthesis of fullerene monoesters and symmetric diesters 8–10 and 11–12, respectively. The synthetic route to the first fullerene–peptide conjugate 16. Synthesis of bioactive fullerene peptides 19 and 20. Synthesis of amino acid–fullerene derivatives 21 and 22. (BtOH is 1H-benzotriazol-1-ol

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• mL column was suspended in 5 mL of DMF and swollen overnight. After washing with DMF (3 × 2 mL), the Fmoc groups of the Rink amide AM resin were activated with 20% of piperidine in DMF (2 mL) for 20 min. After washing with DMF (3 × 2 mL), Fmoc-Ser(t-Bu)-OH (3 equiv) as the first Fmoc-amino acid and

• terminal amino acid, the Fmoc groups of Fmoc-Lys(Fmoc)-OH were activated with 2 × 20% of piperidine in DMF (2 mL) for 20 min, and the coupling reaction with perfluoroalkylated acids (3 equiv) or alkyl acid (3 equiv) was performed 3 times with HBTU/HOBT/DIPEA (6 equiv/6 equiv/12 equiv) for 3 h. After

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• structural, catalytic, energetic, and transport. The introduction of organofluorine components into proteins is typically expected to alter their structure, stability and/or specific features associated with their functional roles [8][9][10][11]. The replacement of natural amino acid residues with the ones

• organisms? In protein evolution, mutations obey a simple "similar replaces similar" rule since the disruption of the resulting protein structure is minimized by the modest changes in the amino acid backbone. Hence, when global substitution of proline is aimed at, it should possibly be ascribed to its

• below. 2.1 Molecular size Replacing hydrogen with fluorine increases the molecular size of congeneric molecules. The molecular volume increases gradually in the row: Pro < Flp < Dfp. However, compared to other amino acid size differences, this increase appears to be quite unspectacular (Figure 3). For

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• resulting telescoped flow process was effectively applied across a series of acid substrates rendering the desired carbamate structures in high yield and purity. The derivatization of these products via complementary flow-based Michael addition reactions furthermore demonstrated the creation of β-amino acid

• into benzyl butyrate in view of facilitating the downstream purification of continuous flow Curtius rearrangement reactions [21]. In this paper, we will give a full account on this valuable approach and showcase the utility of the carbamate products towards generating sets of β-amino acid species

• carbamate group allowing for further use of the resulting N-protected amino acid species (e.g., 9d) in synthetic elaborations. Conclusion In conclusion, a new strategy in continuous flow processing that combines challenging high-energy transformations with downstream impurity tagging facilitated by

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

• introduction of unnatural amino acids into proteins have been reviewed extensively elsewhere [5][6][7] and here we will only discuss the most recent advances. The chemical structures of a selection of 19F-labelled amino acid analogues that have been utilized in 19F NMR studies in chemical biology are shown in

• Figure 1. In general, relatively small monofluorinated amino acids such as 1–4, can be biosynthetically incorporated directly into proteins by including the fluorinated amino acid in the growth medium of a suitable auxotrophic bacterium [8]. However, a challenge when producing 19F-labelled proteins using

• this technique is that the natural amino acid translation process incorporates the specific fluorinated analogue in all the locations where the original amino acid was present, resulting in a “global” labelling of the protein. This can result in a variety of unwanted side effects, including, in some

Supramolecular polymers with reversed viscosity/temperature profile for application in motor oils

• Jan-Erik Ostwaldt,
• Christoph Hirschhäuser,
• Stefan K. Maier,
• Carsten Schmuck and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2021, 17, 105–114, doi:10.3762/bjoc.17.11

• specific viscosity decreases significantly upon increasing the temperature (the same was also observed in toluene solution, see Supporting Information File 1, chapter 6.3.2). Thus, the modification of the linking unit by insertion of one amino acid (to give compound 3) has a detrimental effect on the RVT

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

• interactions [17][18]. By a careful design of the corresponding building blocks, extensive multilateral hydrogen bonds between the amino acid sequences of the oligopeptide backbone lead to secondary structures that direct the equilibrium to polymeric nano-scaled assemblies. A well-studied receptor making use

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• . J. K. Taylor and co-workers reported the first total synthesis of inthomycin B ((+)-2) using a Stille coupling of a stannyl-diene with an oxazole vinyl iodide unit followed by a Kiyooka ketene acetal/amino acid-derived oxazaborolidinone procedure as its cornerstones (Scheme 4) [43]. In the beginning

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• determine the amino acid sequences at the PPIs site. Examples include protein painting [22] and chemical cross-linking [23], hydrogen–deuterium exchange mass spectrometry (HDXMS) [24], and fast photochemical oxidation of proteins [25]. In protein painting, small-molecular dyes are introduced to protein

• amino acid propensities at the protein–protein interface. They discussed that a large portion of the amino acids present at the interface (as large as 75%) are involved in so-called bifurcated interactions, where residues take part in both inter- and intraprotein interactions simultaneously. Both

• homooligomeric complexes can be due to either the interaction of identical amino acid residues or nonidentical amino acid residues on the complex interface, the latter having a similar approach to the heterooligomeric complex residues [69]. Some proteins can form both homooligomeric complexes and

Semiautomated glycoproteomics data analysis workflow for maximized glycopeptide identification and reliable quantification

• Steffen Lippold,
• Arnoud H. de Ru,
• Jan Nouta,
• Peter A. van Veelen,
• Magnus Palmblad,
• Manfred Wuhrer and
• Noortje de Haan

Beilstein J. Org. Chem. 2020, 16, 3038–3051, doi:10.3762/bjoc.16.253

• quantification. Keywords: bioinformatics; cysteine oxidation; glycoproteomics; immunoglobulins; mass spectrometry; Introduction Protein glycosylation mainly occurs in the form of N- and O-glycosylation. N-Glycans are attached to Asn within an amino acid consensus sequence (Asn-Xxx-Ser/Thr, Xxx ≠ Pro) and O

• high complexity of glycosylation itself, data analysis is further complicated by interfering background signals from biological matrices and isomeric and near-isobaric ambiguities resulting from combinations of monosaccharides, adducts, amino acids, and amino acid modifications [10][11]. Efforts have

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• isoindigo 100 was used as substrate, enantioselective [3 + 2] annulation with allene 101 in the presence of amino acid-derived bifunctional phosphine 102 produced adduct 103 in 90% yield with 92% ee and 4:1 regioisomeric ratio (rr). The authors suggested that the observed regioselectivity could be

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• of precisely located functional groups of amino acid sidechains that can codify high-affinity and specific interactions with a target receptor. There are plenty X-ray or NMR structural information available and can be exploited for the rational design of specific peptidic receptors. Integrating an

• insulin Schmuck and co-workers reported a supramolecular ensemble in combination of a pyrene-tagged amphiphilic peptide beacon (6) and a macrocyclic host (cucurbit[8]uril, CB[8]) for ratiometric fluorescent detection of amino acid derivatives, specific peptides, and proteins in aqueous media (Figure 6

• (TrpOMe, PheOMe, LeuOMe) these are found to be more active compared to other amino acid derivatives in displacing 6 from the CB[8] cavity. Similarly, peptides having a hydrophobic amino acid residue at the N-terminus also show a high displacement activity. Human insulin, having a rare Phe residue at the N

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• , and the conversion of the ketoester into an amino acid [2]; and the reaction of aldehydes with either Ph3P/(CF3)2CCl2 [3] or 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane [4][5]. The last method was employed in the synthesis of 16,16,16,17,17,17-hexafluororetinal, as reported by the Haas group [5

Enzyme-instructed morphological transition of the supramolecular assemblies of branched peptides

• Dongsik Yang,
• Hongjian He and
• Bing Xu

Beilstein J. Org. Chem. 2020, 16, 2709–2718, doi:10.3762/bjoc.16.221

• noncovalent synthesis [41][42] in a cellular environment. Results and Discussion Molecular design We designed the branched peptides including the DEXXXLLI sequences [43] for this study. The DEXXXLLI (X is any amino acid) sequences are sorting signals of adaptor protein (AP) complexes, which play a critical

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

• regulate that amino acid sequences are written after “ ; ”, lipid moieties are written after “ : ”, and other glycosides are written after “ # ” (GR1). For example, a glucose β-linked to a Ceramide is written as “Gb:C.” Uncertainty rules describe syntax for when certain features of the SU are unknown or

• Krambeck et al. created, later researchers introduced new attributions that specify and simplify the description of reactions. Bennun et al. and Spahn et al. include the amino acid at the end of the Linear Code attached by a semicolon “ ; ”. This suffix is exactly the syntax from the original Linear Code

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

• the MUC1 VNTR domain. Thus, a synthetic 8-amino acid peptide (APDTRPAP) and the corresponding Tn glycopeptide were synthesized. It was found from the co-crystallization of the AR20.5 antigen-binding fragment (Fab) with the MUC1 peptide and glycopeptide that the glycan moiety of the glycopeptide did

• (physiological temperature). Missing amino acid residues were added. Energy minimization and MD (equilibration and production) simulations were performed using OpenMM [35] and the CHARMM36 force field [36] using the OpenCL platform with mixed precision. Equilibration and production dynamics were carried out as

• simulation. This is defined as the carbon–nitrogen distance between the first and last amino acid residues of the antigen. A time-series analysis provides some insight, while a histogram provides a clearer understanding of the most populated conformations (Figure 3). A Ramachandran plot [41] is a well-known

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

• formed between the charged head group of the encapsulated amino acid and one of the phosphate moieties attached to the tweezer’s central benzene ring [5]. Supramolecular tweezers have not only proven to be interesting tools to modulate protein–protein interactions [6][7], reverse amyloid fibril formation

• negatively charged sulfonate [20][21][22][24][25][27][28][29][30][31][32][34][36][37] or phosphonate [23][33][35] substituents, the aliphatic side chain of the amino acid lines the aromatic bowl-like structure of the calixarene, while the positively charged end group being situated between the sulfonate or

• guanidinocarbonylpyrrole (GCP)-based ligands [41]. GCP mimics the natural amino acid arginine binding to the carboxylate side chains of aspartate (Asp) and glutamate (Glu). The GCP unit provides an extended hydrogen bonding/salt bridge interface, which leads to better binding compared to its natural counterpart. The

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• transformations [7][8][9]. Furthermore, the chiral nature of polysaccharides has also been used as a tool for enantioselective catalysis such as carbonyl hydrogenations and amino acid hydrolysis, proving the unique ability of these biomass-based supports [10][11]. Chitin is another type of biomass feedstock that

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• ://beta.glyco.me/sugarbuilder) is online software for drawing glycans. The interface leads to rapid carbohydrate construction. A panel of monosaccharide templates complements the drawing interface (one pre-built oligosaccharide is available (Figure 8, top). The user can start a chain from amino acid residues: Asn