Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• obtained under controlled reaction conditions, clearly indicated that one amino group (Dab) and three OH groups are present in the toxin. As shown in Table 1, cichorinotoxin has three OH groups in its structure due to the presence of two serine residues and one threonine residue. In addition, one 3

• -hydroxyfatty acid is present, as described above (Figure 2). Thus, there are four OH groups in cichorinotoxin. As mentioned below, the four acetate moieties were determined to be at Dab, the two serine residues and the β-hydroxyfatty acid based on NMR analyses. Thus, the OH group on the Thr residue is blocked

• , is acetylated. The tetraacetate (4), in which the fatty acid, two serine residues (Ser12 and Ser21) and Dab20 are all acylated, had no activity. Ser12, which is present in the linear portion of the peptide, is not conserved in the toxins listed in Supporting Information File 1, Figure S15; thus, it

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• groups capable for the formation of additional hydrogen bonds, both as donors and acceptors. The majority of synthetic strategies starts from natural products and relies on application of chirons having the required configuration at the carbon atom bonded to nitrogen (e.g., serine, glutamic and

• of Subtilisin Carlsberg to give dibenzyl (2R,3S)-N-Boc-3-hydroxyglutamate and (2S,3R)-5-(benzyloxy)-2-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-oxopentanoic acid [25]. The majority of asymmetric syntheses of 3-hydroxyglutamic acid employ serine or similar three-carbon chirons as starting materials

• . Configuration at Cα is retained in the final products and it also induces chirality at the Cβ(OH) center. The hydroxymethyl group of serine can serve as a precursor of the carboxyl fragment but when oxidized to aldehyde it may be attacked by nucleophiles to introduce the required two-carbon residue. From serine

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• modifications of glycocalyx proteins are N-glycans (asparagine-linked) and O-glycans (serine- or threonine-linked), while glycosphingolipids are the major subclass of glycosylated lipids in the cell membrane of human cells (Figure 2). While many core elements of glycocalyx oligosaccharides are conserved between

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• compatibility is of immense versatility since synthesized peptide fragments, which are cleaved from their supports thus freeing the C-terminus, could directly be conjugated to the 5’-terminus of oligonucleotides via tyrosine, serine, or threonine side chains. In order to demonstrate such a versatile conjugation

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• ]. Compared with classical solution-phase peptide synthesis, the fast development of SPPS is mainly due to its short reaction time, high efficiency, low racemization, simple work-up and automation. In recent decades, various strategies, for example, native chemical ligation (NCL) [32] and serine/threonine

• moderate yield (Table 1, entries 3 and 4). Notably, it is unnecessary to protect the hydroxy group of serine, threonine, or tyrosine in advance in the synthesis of these four peptides. The presence of an unprotected hydroxy group does not affect the coupling efficiency, which is consistent with peptide

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

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• . Furthermore, the incorporation of an acetylated lysine instead of the native serine in position 4 decelerated the degradation by α-chymotrypsin which catalyzed the hydrolysis of the peptide bond exclusively between 3Trp and 4Aaa. A similar effect was observed for GnRH-III conjugates in which the ε-amino group

• of 4Lys was acylated by different SCFAs. It is worth to mention that the main cleavage sites of GnRH peptides by different enzymes are at both sides of serine in position 4 [39][40], that can be prohibited by replacement of Ser with an acylated lysine. Moreover, it has been shown that the stability

• that contain 4Lys(Bu) (K2, 4–6) instead of serine indicate a proteolytic cleavage by lysosomal endopeptidases, which might be of great importance for the release of the smallest Dau-containing metabolite. Cytostatic effect of the bioconjugates Cell lines often function as the first model system of

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• green catalysis. Peptide dendrimers including aspartate, histidine and serine were utilized by Reymond et al. as catalytic esterase triad. Using fluorogenic 8-acyloxypyrene-1,3,6-trisulfonates as substrate (Figure 7) at the pH optimum of 5.5, triads’ activity was successfully demonstrated [107]. A

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• such intermediates. By selecting the appropriate reaction conditions (various pH and temperatures), they were able to alkylate free amino acids, e.g., glycine (Gly), L-serine (Ser), L-cysteine (Cys), L-lysine (Lys), L-tyrosine (Tyr) and glutathione (Glu) in aqueous solution to isolate 55 (Scheme 8

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

• -like-peptide-1 (GLP-1), which is an attractive lead compound for the treatment of diabetes mellitus type 2. Unfortunately, the clinical use of the wild-type peptide is severely hampered due to rapid digestion (≈2 min) by the serine protease dipeptidyl peptidase [24][25][26]. Satisfyingly, the

• site and the particular protease [39][40]. Here, we extend these studies to include highly fluorinated, sterically demanding HfLeu, and 5,5,5-trifluoroisoleucine (TfIle) and to investigate their effects on proteolytic stability towards the serine proteases α-chymotrypsin, elastase, and proteinase K

• detailed description of the results for the individual enzymes is given in the following sections. Proteolytic stability towards α-chymotrypsin (EC 3.4.21.1) α-Chymotrypsin is a serine endopeptidase with broad specificity. It preferably cleaves peptide bonds C-terminal to large hydrophobic residues such as

The use of 4,4,4-trifluorothreonine to stabilize extended peptide structures and mimic β-strands

• Yaochun Xu,
• Isabelle Correia,
• Tap Ha-Duong,
• Nadjib Kihal,
• Jean-Louis Soulier,
• Julia Kaffy,
• Benoît Crousse,
• Olivier Lequin and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2017, 13, 2842–2853, doi:10.3762/bjoc.13.276

• Sorbonne Universités, UPMC Univ Paris 06, Ecole Normale Supérieure, PSL Research University, CNRS, Laboratoire des Biomolécules, 4 place Jussieu, 75252 Paris Cedex 05, France 10.3762/bjoc.13.276 Abstract Pentapeptides having the sequence R-HN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine

• proteins aggregation characterized by ordered β-sheet structure assemblies [14][15]. In this context, we synthesized and analyzed, by NMR and molecular modeling, the conformational preferences of eight pentapeptides, containing a L-serine, a L-threonine, a (2S,3R)-L-allo-CF3-threonine or a (2S,3S)-L-CF3

• that the presence of fluorine atoms probably increased the interaction of pentapeptides with Aβ1-42 and their inhibitory effect on Aβ1-42 aggregation. Conclusion We synthesized eight pentapeptides 1a–4a and 1b–4b having the sequence RHN-Ala-Val-X-Val-Leu-OMe, where the central residue X is L-serine, L

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• fluorescence push–pull system would be destroyed. To confirm this, we modified 1 to provide a peptidic substrate for an enzyme. The serine protease DPP-4 was used as the test enzyme because its substrate specificity is clear: it hydrolyses the C-terminal of proline or alanine second to the N-terminal of the

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• propargylamines without an acidifying Cα-substituent. Synthesis of propargylamines containing polar or acidic functional groups The synthesis of propargylamines with polar substituents to mimic polar amino acids such as serine (alcohol), cysteine (thiol) or glutamine (carboxamide) requires special protective

• was successfully applied as protective group to obtain the homologated serine analogous propargylamine 7t similar to the description by Verrier et al. [47][55], starting from TBDMS-protected oxybutanal. Treatment of alkyne 6t with TBAF leads to simultaneous cleavage of both silyl groups. Although

• sterically shielding protective groups have proven convenient, the trityl group turned out to be inefficient to generate a serine-analogous propargylamine. Trityl-protected imine 5m immediately decomposed, when treated with (trimethylsilyl)ethynyllithium. The preparation of glutamic acid-analogous

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• = 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, DPPS = 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine, DPPA = 1,2-dipalmitoyl-sn-glycerol 3-phosphate. Chirally 2H-labelled tripalmitins (1S)- and (1R)-1-[2H]-1 [23]. 1H NMR data and helical conformational properties of tripalmitin 1 and 3-O-benzyl

Enzymatic synthesis of glycosides: from natural O- and N-glycosides to rare C- and S-glycosides

• Jihen Ati,
• Pierre Lafite and
• Richard Daniellou

Beilstein J. Org. Chem. 2017, 13, 1857–1865, doi:10.3762/bjoc.13.180

• retaining mechanism). In the case of O-GTs, the nucleophile is an alcohol or a phenol (carbohydrates, serine, threonine, …), whereas in N-GTs, the nature of the nitrogen-containing group is more diverse (amines, amides, guanidine or even indoles) [12]. S- and C-GTs follow a similar mechanism with the

Selective enzymatic esterification of lignin model compounds in the ball mill

• Ulla Weißbach,
• Saumya Dabral,
• Laure Konnert,
• Carsten Bolm and
• José G. Hernández

Beilstein J. Org. Chem. 2017, 13, 1788–1795, doi:10.3762/bjoc.13.173

• recently investigated the resilience of enzymes under ball milling conditions. The results from these studies have shown that biocatalysts such as cysteine and serine proteases tolerated the milling conditions and catalyzed the mechanoenzymatic peptide and amide bond formation after short milling times

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• different downstream signaling cascades. As the core component of these complexes, mTOR exhibits protein kinase activity and phosphorylates a variety of downstream meditators. One of the principal substrates of the mTORC2 complex is the serine/threonine kinase Akt, which gets activated upon phosphorylation

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• molecular target of PMA was identified in a series of isoforms of PKC, a family of serine/threonine kinases involved in a host of cellular activities [9]. Because of its kinase-activating properties, PMA has become an indispensable tool in the study of cell function, with a single vendor claiming to have

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• which ACP was found in contact with the KS domain [31]. In fungal FAS, ACP is an extended fold comprised of a bacterial-like core fold and a 4-helical extender fold, rendering ACP about twice the size of ACP occurring in mammalian FAS and PKS. The active serine, which is post-translationally

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

• attachment groups and first units involved in energy exchanges [26]. Alternating drying steps followed by rains or floods resulted in the condensation of phosphate moieties on many primeval compounds. These include serine as serine phosphate and aspartate protected against cyclisation as aspartyl phosphate

G-Protein coupled receptors: answers from simulations

• Timothy Clark

Beilstein J. Org. Chem. 2017, 13, 1071–1078, doi:10.3762/bjoc.13.106

• . GPCRs are normally deactivated by β-arrestin, as shown in Figure 4. After activation and dissociation of the β/γ subunit, IL3 and the C-terminus of the GPCR are phosphorylated at serine and threonine residues (Figure 4a). This phosphorylation allows the recruitment of β-arrestin (Figure 4b), which can

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• numbering) capable of forming salt bridges with the carboxyl group of the building block, while these are non-polar amino acids in starter-unit specific ATs. The choice of methylmalonyl-CoA over malonyl-CoA is correlated with a YASH motif some 100 residues downstream of the active site serine, whereas

• extension. Based on the presumed biosynthetic origin of these extender units (from L-serine and from a glycolytic intermediate (in all likelihood 1,3-biphospho-D-glycerate), respectively), it was initially proposed that the (2S)-isomer of aminomalonyl-ACP and the (2R)-isomers of hydroxyl-/methoxymalonyl-ACP

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

• has occurred at an internal tryptophan residue of the precursor peptide. Kawaguchipeptin A Apart from the ComX pheromones, post-translational dimethylallylations of the tyrosine, threonine, serine, and tryptophan residues of cyclic peptides from cyanobacteria were reported [49][50][51]. The RiPPs

Solution-phase automated synthesis of an α-amino aldehyde as a versatile intermediate

• Hisashi Masui,
• Sae Yosugi,
• Shinichiro Fuse and
• Takashi Takahashi

Beilstein J. Org. Chem. 2017, 13, 106–110, doi:10.3762/bjoc.13.13

• serine, and the subsequent reduction of carboxylic acid derivatives such as ester [20][21][22][23][24][25][26][27], thioester [28], or Weinreb amide [29][30] to the aldehyde. In addition, Burke and co-workers reported an asymmetric hydroformylation of 2,2-dimethyl-2,3-dihydrooxazole for the synthesis of