Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• < 5%) despite numerous attempts. Conclusion This work described the stereoselective and gram-scale synthesis of a highly attractive palette of fluorinated amino acids prepared for application in solid-phase peptide synthesis. First, two different fluorinated variants of phenylalanine were synthesized

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• molecules Aside from an analysis of the BB usage pattern, real NRP-like molecules can be constructed in accordance to the predicted identity and order of the BBs. Brady and co-workers used solid-phase peptide synthesis to convert the predicted NRPs from virtual into reality; they called these molecules

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• beads, the beads can be split into two portions from which one is analyzed by in-gel analysis first to determine the overall labeling and the other portion after on-beads trypsin digest is subjected to LC–MS/MS analysis. The AzKTB reagent can be synthetized by standard solid-phase peptide synthesis

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• . Additionally, stereoselectivity can be achieved by using potassium bis(trimethylsilyl)amide for deprotonation and methylation with MeI [33][39]. Any of these routes would yield methylated amino acids that can then be incorporated into an oligopeptide in solid-phase peptide synthesis (SPPS). Additionally, N

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• attention is given to the strategies of mimics formation to demonstrate how biocatalysis provides an elegant link between chemistry and biology. Review Macrocyclic peptides Since first being reported in the 1960s [26], solid-phase peptide synthesis (SPPS) has been an invaluable tool for preparing numerous

• aforementioned NPRS macrocycles, the synthesis of macrocylic polyketides and PKS/NRPS hybrids is more challenging due to the absence of a streamlined preparation strategy such as solid-phase peptide synthesis (SPPS). In enzymology studies, it was common to hydrolyze the cyclic natural products in order to obtain

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• scale [19], and linkers [20][21] affect the overall yield of solid phase peptide synthesis (SPPS). In the past decades, several supports and linkers have been developed and commercialized for SPPS, enabling a wide range of applications. Solid supports are available with different linker loadings, with

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• microbial world. To elucidate the role of compounds 1–4 in the microbial world, developing a strategy to synthesize compounds 1–4, including future derivatization to produce probe molecules, is required. Herein, we report the total synthesis of peptide 1 by Fmoc-based solid-phase peptide synthesis [9] and

• with stereocontrol. Then, the peptide chain was elongated by Fmoc-based solid-phase peptide synthesis. Finally, the cyclization of the peptide chain followed by simultaneous cleavage of all protecting groups in the solution phase afforded target compound 1. The comparison of the chromatograms of

• communication in the microbial world. Herein, we report the solid-phase total synthesis and structural confirmation of longicatenamide A. First, commercially unavailable building blocks were chemically synthesized with stereocontrol. Second, the peptide chain was elongated via Fmoc-based solid-phase peptide

Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

• Qiuxin Zhang,
• Weiyi Tan and
• Bing Xu

Beilstein J. Org. Chem. 2022, 18, 159–166, doi:10.3762/bjoc.18.17

• solid-phase peptide synthesis (SPPS) to generate the peptide segments ((G/GG/GGG)ffpy for 2a–h, 9, 10a,b, GGGFFpY for 3a,b, GGGffps for 4a,b, GGGffpS for 5a,b, aaaffpy for 6a–c, rffpy for 7, GGllllpy for 8a,b, GGGffy for 11a,b, aaaffy for 12a–c, NBD-ffky for 13, NBD-ffkpy for 14, GG(G) for 15a–c). Then

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

• organoboron containing side chain in the i + 4-position. The peptides were synthesised on Rink amide resin by solid-phase peptide synthesis (SPPS) with Fmoc/t-Bu strategy followed by on-resin SMC. For the cross-coupling, a modified protocol by Planas and co-workers was used [78]. Pd2(dba)3 was employed as the

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• -sensitive Plasmodium falciparum. Herein, we describe the first total synthesis of hoshinoamide A by the combination of liquid-phase and solid-phase peptide synthesis. Liquid-phase synthesis is to improve the coupling yield of ʟ-Val3 and N-Me-ᴅ-Phe2. Connecting other amino acids efficiency and convergence is

• in Scheme 1, we initially tested Fmoc solid-phase peptide synthesis (SPPS) [13] to get 2-chlorotrityl resin-bound Pro1-(N-Me)-Phe2 dipeptide 2 under the conditions of HCTU and DIPEA. Unfortunately, the N-Me coupling proceeded in low yield (<10%). In order to improve the coupling yield of the hindered

• –90 vol % MeCN over 30 min, 90–90 vol % over 10 min, 90–10 vol % MeCN over 10 min) at a flow rate of 8 mL/min. Standard SPPS (solid-phase peptide synthesis) method: General procedures for coupling on resin: The loaded resin was shaken for 2 h at room temperature with a solution of the desired Fmoc-AA

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

• ’-flouronated base; italics and underlined = 2’-O-methyl base Complementary DNA A-1: (Cy5/AGG CTA TCT AGA ATG TAC) G-3: (Cy5/TCT ATC AAT CTA TCA) Peptide synthesis, purification, and characterization Peptide assembly was carried out by solid-phase peptide synthesis in standard solid-phase extraction filtration

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

• . By contrast, the hydrocarbon lipopeptide led to microbubbles with a larger mean diameter and a significantly lower stability. Keywords: adsorption at fluid interfaces; drug delivery; microbubble targeting; molecular imaging; monolayer; perfluoroalkylated lipopeptide; solid-phase peptide synthesis

• safety [15][16][17]. Various effective receptor-binding peptides have been identified by the phage display technology [18]. The peptides can be readily prepared through solid-phase peptide synthesis (SPPS), a highly reproducible method with minimal side reactions. Many peptide–lipid conjugates

• (SG)5KSS peptide chain is assembled stepwise using a Fmoc solid-phase peptide synthesis procedure. In a second step, the two perfluoroalkylated chains are grafted to the peptide chain through a lysine moiety. Next, the surface activity of the synthesized lipopeptides is investigated by assessing their

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

• -phase peptide synthesis (SPPS) methods (15 and 16, Figure 1). A second well-established methodology for the 19F isotopic labelling of protein and peptides involves the post-translational chemical conjugation of an 19F probe to specific amino acids present within the protein, typically cysteine and

• aliphatic amino acid, (E)-2-amino-5-(pentafluorosulfanyl)pent-4-enoic acid (14, Figure 1), SF5NVa [21]. Most recently, Cobb et al. [22] reported the synthesis of several pentafluorosulfanyl phenylalanine derivatives with suitable protecting groups to allow incorporation into peptides through common solid

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

• form the branched peptide 1. To investigate how the acetylation of aspartic acid affects the proteolysis and the formation of assemblies, the acetylation of the N-terminal of the branch in 1 would generate 2. Synthesis We used 2-chlorotrityl chloride resin for the typical Fmoc solid-phase peptide

• synthesis (SPPS) [47] to produce the peptides shown in Scheme 1. We first synthesized the peptide segments (i.e., Fmoc-DEDDDLLIG (1a) and acetyl-DEDDDLLIG (2a)). We kept the tert-butyl protecting groups of aspartic acid for the coupling reaction with Nap-ffky. We used 2,2,2-trifluoroethanol (TFE) in

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

• development of novel drug nanocarrier assemblies. Keywords: aqueous self-assembly; pH-responsive systems; secondary structure; self-assembled nanostructures; solid-phase peptide synthesis; Introduction The self-assembly of small molecules is a ubiquitous phenomenon in nature [1] and also has key

• nanostructures as well as the secondary structures. Results and Discussion Solid-phase peptide synthesis and purification The target octapeptide was synthesized in the solid phase following four steps, including: i) deprotection of the Fmoc protecting group, ii) coupling of an amino acid, iii) cleavage of the

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• have been synthesized via solid-phase peptide synthesis and SN2’ reaction on a Morita–Baylis–Hillman (MBH) residue introduced at the N-terminal of a tetrapeptide. This last step takes advantage of the electrophilic feature of the MBH residue and represents a new cyclization strategy occurring. The

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

• (O)Ac N-terminal), 170.0 (C(O) Gal), 172.2 (C(O) Ala4), 172.7 (C(O) Ala5), 172.8 (C(O) Ala1), 173.2 (C(O) Ala2). Glycosylated building blocks prepared for solid phase peptide synthesis (SPPS). Model AFGP analogues. Conformational preferences of investigated glycopeptides. Conformational preferences

Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer

• Sagnik Sengupta,
• Mena Asha Krishnan,
• Premansh Dudhe,
• Ramesh B. Reddy,
• Bishnubasu Giri,
• Sudeshna Chattopadhyay and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244

• successfully designed and demonstrated a novel continuous process for assembling targeting ligands, peptidic spacers, fluorescent tags and a chelating core for the attachment of cytotoxic molecules, radiotracers, nanomaterials in a standard Fmoc solid-phase peptide synthesis in high yield and purity. The

• tag; Fmoc-Lys-(Tfa)-OH; prostate cancer and ovarian cancer; solid-phase peptide synthesis; Introduction The understanding of cell processes is indispensable to devise new strategies for diagnosis and treatment of cancer and inflammatory diseases through targeted drug delivery techniques [1]. The

• ligand for biomarkers, a fluorescent tag and a chelating moiety for tethering cargo in a continuous process using solid-phase peptide synthesis is poorly developed. Traditional solid-phase peptide synthesis methods for preparation of bioconstructs employ orthogonally protected functional moieties present

Comparative cell biological study of in vitro antitumor and antimetastatic activity on melanoma cells of GnRH-III-containing conjugates modified with short-chain fatty acids

• Eszter Lajkó,
• Sarah Spring,
• Rózsa Hegedüs,
• Beáta Biri-Kovács,
• Sven Ingebrandt,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 2495–2509, doi:10.3762/bjoc.14.226

• antiproliferative/cytotoxic activities, the cell adhesion and migration modulator effects of conjugates and their ability to induce apoptosis or cell cycle arrest in A2058 melanoma cell line. Results and Discussion Synthesis of Dau–GnRH-III conjugates The modified GnRH-III derivatives were prepared by solid phase

• peptide synthesis (SPPS) using Fmoc/t-Bu strategy with the orthogonal protecting scheme as described before [17][19] and presented in detail in Supporting Information File 1. In all cases, a Mtt (methyltrityl) protecting group was applied to block the side chain of Lys in position 8. For the development

Defining the hydrophobic interactions that drive competence stimulating peptide (CSP)-ComD binding in Streptococcus pneumoniae

• Bimal Koirala,
• Robert A. Hillman,
• Erin K. Tiwold,
• Michael A. Bertucci and
• Yftah Tal-Gan

Beilstein J. Org. Chem. 2018, 14, 1769–1777, doi:10.3762/bjoc.14.151

• ), homophenylalanine (hPhe), or Tyr; Figure 3). The CSP1 analogs were constructed using standard solid-phase peptide synthesis (SPPS) protocols (see Materials and Methods for SPPS procedures), followed by purification to homogeneity by semipreparative RP-HPLC (see the Supporting Information File 1 for full

• . All the CSP1 analogs were synthesized on a 4-benzyloxybenzyl alcohol (Wang) resin (0.65 mmol/g) pre-loaded with Fmoc-L-Lys(Boc). With the exception of the phenylglycine and norvaline derivatives, the CSP1 analogs were synthesized using standard Fmoc-based solid-phase peptide synthesis (SPPS

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

• , purification and analysis Peptides were synthesized by solid-phase peptide synthesis on Rink Amide resin, with a substitution degree of 0.52 mmol g−1 on a 0.1 mmol scale, using the Fmoc strategy on a peptide synthesizer (PS3 – Protein Technologies) as described by Torres et al. [9][10]. Dry-protected peptidyl

Drug targeting to decrease cardiotoxicity – determination of the cytotoxic effect of GnRH-based conjugates containing doxorubicin, daunorubicin and methotrexate on human cardiomyocytes and endothelial cells

• Livia Polgár,
• Eszter Lajkó,
• Pál Soós,
• Orsolya Láng,
• Marilena Manea,
• Béla Merkely,
• Gábor Mező and
• László Kőhidai

Beilstein J. Org. Chem. 2018, 14, 1583–1594, doi:10.3762/bjoc.14.136

• here are shown in Figure 1 and Figure 2. The GnRH derivatives were prepared by solid phase peptide synthesis (SPPS) according to Fmoc/t-Bu strategy (Supporting Information File 1). Three drug molecules, doxorubicin (Dox), daunorubicin (Dau) and methotrexate (Mtx), were employed in the preparation of

Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• sequences, as well as sC18* alone. All peptides were readily synthesized via Fmoc/t-Bu solid-phase peptide synthesis, purified, and analyzed by LC–MS methods as previously described [19][20]. Moreover, 5(6)-carboxyfluorescein (CF)-labeled versions were generated (Table 1). As shown in Table 1 and Figures S1

• synthesized using a combination of standard Fmoc/t-Bu solid-phase peptide synthesis (SPPS) on a Syro I peptide synthesizer (MultiSynTech, Bochum, Germany) and manual coupling protocols according to previous works [17][19][20]. Peptides were generated on a Rink amide resin (loading 0.48 mmol/g) yielding C

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

• ) reagent FPID and (4-MeOC6H4)3P was successfully applied to solid-phase peptide synthesis and cyclic peptide synthesis. Four peptides with biological activities were synthesized through SPPS and the bioactive cyclic heptapeptide pseudostellarin D was obtained via solution-phase peptide synthesis. It is

• worth noting that FPID can be readily regenerated after the peptide coupling reaction. Keywords: cyclic peptide; FPID; hypervalent iodine(III) reagent; recyclable; solid-phase peptide synthesis (SPPS); Introduction The amide bond is one of the most fundamental functional groups in organic chemistry

• peptide synthesis and cyclic peptide synthesis. Results and Discussion At the beginning of our study, we tried to utilize the system of FPID/(4-MeOC6H4)3P in the solid-phase peptide synthesis (SPPS). SPPS has been widely employed in peptide synthesis since its first report by Merrifield in 1963 [30][31