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

• additional ethylene unit in the linker suggested a conformation with the highest similarity to the linear reference peptide P6 (see Supporting Information File 1), thus representing a good compromise between rigidity and preservation of the target secondary structure. Serine in i-position and glutamic acid

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• in good yields (Scheme 39C). The authors used the same methodology to synthesize two 4H-benzo[d][1,3]oxazin-4-one derivatives that act as inhibitors of two enzymes (compounds 130 and 131 in Scheme 39D). The first one is the enzyme C1r serine protease, involved in both inflammation and renal scarring

A systems-based framework to computationally describe putative transcription factors and signaling pathways regulating glycan biosynthesis

• Theodore Groth,
• Rudiyanto Gunawan and
• Sriram Neelamegham

Beilstein J. Org. Chem. 2021, 17, 1712–1724, doi:10.3762/bjoc.17.119

• -value = 0.035). SMAD proteins are activated by TGF-β signaling and bind to DNA to act as cofactors to recruit TFs. SMAD2 has been shown to act as a tumor metastasis suppressor in cell lines [32][33]. This TF was found to regulate GALNT1 (ρ = 0.54, RP = 1.00), which adds GalNAc to serine or threonine

• the addition of GlcNAc to processed N-linked glycan structures. These include all the MGAT enzymes. 7) GalNAc-type O-glycans: O-linked glycans are attached to serine (Ser) or threonine (Thr) on peptides, where GalNAc is the root carbohydrate. This is mediated by a family of about 20 Golgi-resident

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

• –dsRNA triplexes [74]. γ-Modified PNA: Later studies focused on introducing substituents in the ethylenediamine moiety of the PNA backbone. Ly and co-workers showed that introduction of simple substituents, such as methyl (derived from ʟ-alanine) or hydroxymethyl (derived from ʟ-serine) at the γ-position

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• , and serine derivatives were proceeded to extend the scope of the reaction (Scheme 13) [44]. An efficient domino three-component route has been developed for the synthesis of fully decorated 1,2,3-triazoles 38 bearing a sulfonyl group in position 4. The synthesis required aldehydes 35, amines 36, α

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

• serine–glycine (SG)n segments rather than classical poly(oxyethylene) linkers between the lipid polar head and a targeting ligand were proposed for the liposome-mediated, selective delivery of anticancer drugs. Here, we report the synthesis of perfluoroalkylated lipopeptides (F-lipopeptides) bearing two

• hydrophobic chains (CnF2n+1, n = 6, 7, 8, 1–3) grafted through a lysine moiety on a hydrophilic chain composed of a lysine–serine–serine (KSS) sequence followed by 5 SG sequences. These F-lipopeptides are precursors of targeting lipopeptide conjugates. A hydrocarbon counterpart with a C10H21 chain (4) was

• proposed for the preparation of functional drug carriers for clinical applications [25][28][29]. In order to alleviate the steric hindrance effect of PEG chains, a novel spacer consisting of alternating serine–glycine sequences (SG)n was introduced between the ligand and lipid within the molecular

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

• -containing proteins. How could it happen that the stability is affected but the structure is not? First of all, in contract to classical mutations (e.g., the replacement of proline with serine), a substitution of an amino acid by a fluorinated analogue generates very little disturbance to the structure

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• preparation of bioactive compounds with potential antioxidant properties [2][3][4][5]. Operating via a two-step serine protease mechanism involving a conserved Ser-His-Asp/Glu catalytic triad [6][7], Faes catalyze the hydrolysis of ester bonds linking hydroxycinnamoyl groups to the glycosyl moieties of plant

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

• interactions but have a high propensity to form interprotein interactions. In contrast, serine, threonine, asparagine (polar uncharged), alanine, valine, isoleucine (hydrophobic), cysteine, proline, and glycine are less likely to form interprotein interactions and bifurcated interactions. The binding mode in

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

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

• serine protease of human mast cells and is known to be involved in the pathogenesis of asthma and other allergic and inflammatory disorders [48][49][50]. The structure of the enzyme is tetramer, composed of four identical subunits arranged in two different orientations, around a central pore. In vivo

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

• 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

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• compared to a benzyl substituent [18]. The deleterious effect of a substituent α to the amine was most pronounced in the case of alanine (product 13), as compared to glycine (product 2). However, this steric constraint could be largely overcome by the presence of a β-hydroxy group, as seen with serine

• entirely unreactive under the typical reaction conditions. In this case the reaction required 3 h at 130 °C before product formation was observed. Interestingly, much like the improved results for serine, a β-hydroxy group dramatically overcame this issue for secondary amines, as 2-(methylamino)ethanol

• ion pairs with the cationic DBU-activated acyl intermediate (see Figure 1). However, the α-substitution in alanine clearly abolishes any rate acceleration driven by ionic interactions, and most α-substituted amines had similar rates. Rate acceleration is recovered in serine, owing to the effect of the

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• benzyl protected serine at the Dha site. Following hydrogenolytic deprotection, in situ produced serine EDC adduct was subjected to copper(I) chloride-mediated elimination to give the dehydroalanine derivatives 34a and 34b in good yields. Deprotection of the ester protecting group also proceeded in good

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• these organisms. C-Methylation at C9 of fungal sphingosines is similarly catalyzed by SAM-dependent methyltransferases [16]. The methylation takes place at the alkenyl carbon (C9) which is originally derived from the carbonyl carbon of an acetate unit: C1 and C2 of sphingosines are derived from ʟ-serine

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• could be prepared from ᴅ-mannitol. While derivatives of glyceraldehyde are configurationally stable Garner’s aldehyde 3a [8][9], available from ʟ-serine, is configurationally labile and samples with ee as low as 75% can be obtained depending on the reaction conditions. Significant improvement in terms

• by transforming enantiomerically pure (2R,1'S)-5a and (2S,1'S)-5a into (R)- and (S)-serine, respectively (Scheme 2) [13][16]. Synthesis of N-(1-phenylethyl)aziridine-2-carbaldehydes 6 Aziridine aldehydes 6 are in most instances prepared from the corresponding alcohols 7 by Swern oxidation [28][29][30

• )-5a was reacted with 3-bromo-5-methoxy-1H-1,2,4-triazole (128) to give N-protected bicyclic amino ester 129 which was next converted into (S)-(+)-127 in two standard steps (Scheme 33) [17]. Its enantiomer was prepared from (2R,1′S)-5a. Lacosamide ((R)-130) is a derivative of ᴅ-serine and has found

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• the serine residue and the amide proton of GalNAc unit [33]. This correlates with our results obtained for longer peptides containing the same sugar moiety attached to threonine. Moreover, Corzana et al. [33] highlighted the importance of surrounding solvent molecules, which are responsible for the

• determined, no predominant conformer was found. As shown in Figure 3A and B both tripeptides indicate a fully flexible conformation. Corzana et al. suggested for the C- and N-protected, glycosylated ʟ-serine residue an extended conformation without intramolecular hydrogen bond between the amide proton of

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• Scheme 4, the authors developed methods for the functionalization of spirostanic steroids and their further conjugation to amino acids by means of the Ugi-4CR. Thus, seco-steroidal amine 10 – derived from the steroidal sapogenin hecogenin (9) – was ligated to Boc-protected serine in presence of

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

• Robert J. Kempton,
• Taylor A. Kidd-Kautz,
• Soizic Laurenceau and
• Stefan Paula

Beilstein J. Org. Chem. 2019, 15, 971–975, doi:10.3762/bjoc.15.94

• cytotoxic agent. The problem of concomitant toxicity to healthy cells has been circumvented by attaching a short peptide (His-Ser-Ser-Lys-Leu-Gln-Leu) to a tether at TG’s C-8 position (1b). This modification renders the inhibitor inactive [3]. Prostate cancer cells produce on their surface the serine

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• described as a potent inhibitor of various proteases, in particular trypsin and thrombin [17][18][19]. Hereby, the α-keto amide covalently binds to the serine oxygen in the active site under formation of a stable tetrahedral hemiketal. Furthermore, substitution of the indole hydrogen by alkyl, aryl or

• , the azaindole derivatives are currently under investigation upon their use for fluorescence imaging. Furthermore, derivatives 3 and 6 will be further studied for identification of their actual target in S. aureus. This could be a serine protease that can also be addressed in the future by more stable

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• [70]. α-Chymotrypsin is a serine protease that recognizes hydrophobic residues in one of its clefts. A modified HG-type catalyst (66) contains an L-phenyl chloromethyl ketone moiety that acts as inhibitor and is first recognized by supramolecular anchoring and then covalently attaches upon

• , entries 2, 7 and 12). Gebbink and co-workers anchored the HG-type catalyst 79 to cutinase, a serine hydrolase [75]. The phosphonate ester moiety acts as a suicide inhibitor forming an irreversible covalent bond to a serine residue present in the active site of the enzyme. Assembly of ArM 8 occurs at pH 5

Synthesis of C₃-symmetric star-shaped molecules containing α-amino acids and dipeptides via Negishi coupling as a key step

• Sambasivarao Kotha and
• Saidulu Todeti

Beilstein J. Org. Chem. 2019, 15, 371–377, doi:10.3762/bjoc.15.33

• ) derivatives and dipeptides. In this regard, trimerization and Negishi cross-coupling reactions are used as the key steps starting from readily available 4’-iodoacetophenone and L-serine. These C3-symmetric molecules containing AAA moieties are useful to design new ligands suitable for asymmetric synthesis and

• . Results and Discussion The required zinc insertion compound 7 was prepared from L-serine (3). Thus, commercially available L-serine (3) was treated with acetyl chloride in methanol to give methyl ester 4, which was subjected to N-Boc protection with di-tert-butyl dicarbonate (Boc2O) and triethylamine in

• tetrahydrofuran (THF) to obtain the N-Boc-serine methyl ester (5) in 93% yield [42]. Afterwards, the protected methyl ester 5 was subjected to iodination in the presence of iodine (I2), triphenylphosphane (PPh3) and imidazole in CH2Cl2 at 0 °C to deliver the iodo derivative 6 in 63% yield [43][44]. Finally, the

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