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

• –oligo-Lys (5a), was purified by reversed-phase HPLC, while C60–oligo-Glu (5b) was purified by spin filtration. C60–oligo-Lys (5a) was obtained in a yield of 32% for the total peptide synthesis and characterized by HRESIMS. HRESIMS (m/z): [M + 3H]3+ calcd for C135H148N23O16, 782.3819; found, 782.3821

• . C60–oligo-Glu (5b) was obtained in a yield of 36% for the total peptide synthesis and characterized by HRMS–MALDI. HRMS–MALDI (m/z): [M + H]+ calcd for C125H96N13O36, 2354.6075; found, 2354.6008. C60–oligo-Arg (5c) was obtained in a crude yield of 66% for the total peptide synthesis and characterized

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

Palladium-catalyzed enantioselective three-component synthesis of α-arylglycine derivatives from glyoxylic acid, sulfonamides and aryltrifluoroborates

• Bastian Jakob,
• Nico Schneider,
• Luca Gengenbach and
• Georg Manolikakes

Beilstein J. Org. Chem. 2023, 19, 719–726, doi:10.3762/bjoc.19.52

• decrease of the isolated yields. As already demonstrated in our previous work, the Pbf-protected arylglycine products can be directly used as building blocks for peptide synthesis [22]. Finally, we utilized our method for the preparation of a protected version of p-hydroxyphenylglycine (Scheme 5), a common

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

A versatile way for the synthesis of monomethylamines by reduction of N-substituted carbonylimidazoles with the NaBH₄/I₂ system

• Lin Chen,
• Xuan Zhou,
• Zhiyong Chen,
• Changxu Wang,
• Shunjie Wang and
• Hanbing Teng

Beilstein J. Org. Chem. 2022, 18, 1032–1039, doi:10.3762/bjoc.18.104

• particularly suitable for peptide chemistry since protecting groups are often required in peptide synthesis [52][53]. These multistep reaction methods are conducive to avoid overmethylation products. Although procedures for the synthesis of monomethylamines have been developed over the past years, the starting

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

• , 1 h. In panel C), amino acids in R1 and R2 are with protecting groups and R2 is resin-bound (Rink amide resin); R3 = 4-phenylboronic acid or (4-ethylphenyl)boronic acid (P2–P5). Supporting Information Supporting Information File 6: Details on the amino acid and peptide synthesis, analytical data of

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• frequently adopted. For example, in peptide synthesis, peptides with acid-labile side chain protections can be selectively cleaved from the acid-labile 2-chlorotrityl resin with dilute TFA [34]. In RNA synthesis, the acid-sensitive 2'-TOM protecting groups can survive the acidic conditions for removing the 5

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

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

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• transformation in this case. After several failed attempts, a procedure typically used for Boc deprotection in peptide synthesis utilizing TFA and triisopropylsilane was successfully used. Product purification furnished the desired enantiomer of pavettamine as a TFA salt (28). The presence of TFA was evident in

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

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

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• with Selectfluor® [153]. The authors justified the use of protecting groups due to their extensive use in peptide synthesis. Of all the PGs tested, phthalimide (Phth)- and trifluoroacetate (TFA)-protected substrates underwent photosensitized C–H fluorination to give the highest yield of 80% and 71% of

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

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• peptide synthesis technology [3][4] have enabled peptide production at industrial scales, the exploration of therapeutic peptides as potential drugs is rapidly developing [4][5][6]. It has been shown that peptide drugs are less immunogenic than biologics and can hit the “undruggable” space of molecular

• to their original design in [30]. Acknowledgements We thank Dr. Wadhwani (KIT, Karlsruhe) for access to the peptide synthesis facility. Funding Financial support was provided by Helmholtz Association (Germany) via the program “BioInterfaces in Technology and Medicine” (BIF-TM). SA, OB, IVK, and ASU

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

• sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence ᴅ-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide. Keywords: antibiotic; argyrin

• ; mutasynthesis; NRPS; peptide synthesis; Introduction Resistance to antibiotics is currently a major threat to public health. Especially Gram-negative bacterial pathogens are of concern, due to their widespread development of resistance mechanisms. To address this general antimicrobial resistance problem, new

• Helmholtz Association (HGF, grant no. VH-NG-934), the European Research Council (ERC StG, grant no SWEETBULLETS) and the German Centre for Infection Research (DZIF) is acknowledged. Author Contributions Statement D.C.B.S. and R.S. designed and performed peptide synthesis. D.P. and S.C.W. designed and

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

• , agriculture, biomedical cryopreservation [22][23][24]. Results and Discussion Peptide synthesis Starting from ᴅ-(+)-galactose, we obtained the 3,4,6-tri-O-acetyl-ᴅ-galactal in an excellent yield and transformed it into 3,4,6-tri-O-acetyl-2-azido-2-desoxy-α-ᴅ-galactopyranosyl chloride by one pot

• (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

Synthesis of a tubugi-1-toxin conjugate by a modulizable disulfide linker system with a neuropeptide Y analogue showing selectivity for hY1R-overexpressing tumor cells

• Rainer Kufka,
• Robert Rennert,
• Goran N. Kaluđerović,
• Lutz Weber,
• Wolfgang Richter and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2019, 15, 96–105, doi:10.3762/bjoc.15.11

• three cell lines was determined as proof for targeted delivery. Results and Discussion Synthesis of tubugi-1 building blocks We established the Ugi reaction as a powerful tool for peptide synthesis and ligation, including the first syntheses of tubulysine derivatives by us and later also others [44][53

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

• 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