Amino acid-based surfactants: sustainable synthesis and antimicrobial mechanisms

• Rafaela Gomes Bezerra,
• Lourdes Pérez and
• Francisco Fábio Oliveira de Sousa

Beilstein J. Org. Chem. 2026, 22, 1067–1085, doi:10.3762/bjoc.22.85

• preservation at physiological conditions, and their compatibility with delivery-system strategies [82][83]. Individually or combined, other amino acids such as lysine [68][84], tryptophan, phenylalanine [4][59], glycine [85], serine [86], cysteine, histidine, leucine and valine [56][87] are also used to

One-pot four-component sequential synthesis of S-alkyl dithiocarbamates using lipase as a biocatalyst

• Mansour Shahedi,
• Pargol Tahmasebi pour and
• Zohreh Habibi

Beilstein J. Org. Chem. 2026, 22, 1048–1056, doi:10.3762/bjoc.22.83

• the aldehyde, resulting in the formation of the intermediate 8a. Next, the ester portion of the ketoester is hydrolyzed through the serine amino acid, leading to the formation of the intermediate 9a. This intermediate then undergoes decarboxylation, which can be assisted by histidine or aniline

Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• exhibits a broad substrate scope, high efficiency, excellent functional-group tolerance, and consistently high levels of deuterium incorporation (Scheme 5Bi) [100][101]. Notably, the transformation proceeds efficiently with derivatives of biologically active molecules, such as serine and niflumic acid

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• -like linkages (≈9 M−1 s−1; Scheme 1d) [10], whereas 2-formylphenylboronic acid 3 (FPBA) generates thiazolidino boronate with noticeably improved kinetics (103 M−1 s−1; Scheme 1e) [11][12]. Aldehydes can be introduced at protein N-termini through several strategies: oxidation of serine or threonine with

• sodium periodate (Scheme 2a) [13], selective modification of glutamate using Rapoport’s salt (4) which has generated modified trastuzumab in moderate yield (67%; Scheme 2b) [14], or pyridoxal phosphate (PLP, 5)-mediated carbonyl formation at residues such as serine, threonine, glycine, alanine, or

• biological environment [46]. In a related concept, the Chin group reported the genetic incorporation of the unnatural amino acid 2,3-diaminopropionic acid (DAP, 13), a nucleophilic amine that has a relatively low pKa (6–8) and is structurally analogous to serine or cysteine, enabling identification of native

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• -serine, ʟ-methionine, β-naphthylalanine, phenylglycine, 4-iodophenylalanine, on the achiral Cu(I)/L17 complex leads to the formation of enolates with copper-centered chirality in the form of complex D. Next, complex D interacts with dipolarophiles 53, including fumaronitrile, N-substituted maleimides, β

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• overall selectivity of PROTACs, utilizing several high-profile targets as illustrative examples. CDK Cyclin-dependent kinases (CDKs) are members of the serine/threonine (S/T) kinase subfamily comprising 21 CDK enzymes [44]. CDK1, 2, 3, 4, and 6 play a key role in cell cycle regulation. CDK7, 8, 9, and 11

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• Cambridge Institute, Robinson Way, Cambridge, CB2 0RE, United Kingdom 10.3762/bjoc.22.47 Abstract Human protein kinase CK2 is a constitutively active serine/threonine kinase implicated in numerous cancers. Although ATP-competitive inhibitors such as CX-4945 show therapeutic potential, they are limited by

• regulate key cellular processes through the phosphorylation of protein substrates. Dysregulation of kinase activity, often through mutation or altered expression, is associated with numerous malignancies [1]. CK2 (previously called casein kinase 2), a constitutively active serine/threonine kinase

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• inhibits glutaminase by covalently labeling the catalytic serine [8]. DON inhibits other glutamine-utilizing enzymes such as asparagine synthetase and has activity against a wide range of cancer cell lines [9][10]. BPTES is a potent allosteric inhibitor of GAC/KGA that binds at the dimer–dimer interface

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• prenylindoles (Figure 1, approach B) which would rely on a Negishi cross-coupling reaction [37][38] using Jackson’s iodozinc N-Boc-ʟ-serine methyl ester [39] and 3-iodoallyl- or 3-iodoprenylindoles (Figure 3). Related Negishi cross-coupling reactions have been reported for bromoindoles [40] and 3-iodo-N-Boc-7

• amino acid reagent that could be removed under non-acidic conditions after the cross-coupling reaction. To this end, we prepared iodo N-Fmoc-ᴅ-alanyl anthranilamide methyl ester 29 from ᴅ-serine. Treatment of prenylindoles 14–17 with iodine and KOH followed by acetylation afforded the corresponding

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• . Lipases commonly share typical sequences of α-helices and β-strands and possess a catalytic triad consisting of serine (Ser), histidine (His), and aspartate (Asp) or glutamate (Glu). These three amino residues function as a nucleophile-base–acid catalytic system to facilitate esterification, and the

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• the synthesis of structurally diverse reactive probes bearing S(VI) electrophiles. Proteome-wide screens have shown that S(VI) electrophiles predominantly target lysine and tyrosine [12], although other residues (e.g. serine) may also be targeted within enzyme active sites [13]. It was envisaged that

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• HSA in aqueous medium shows a characteristic oxidation wave that begins to rise around +0.5 V and significantly increases up to +1.2 V vs Ag/AgCl (Figure 3). This wave is attributed to oxidation processes at peptide bonds or specific side chains (such as cysteine, methionine, tyrosine, serine

• . When these agents alkylate the HSA amino acid residues (particularly reactive sites like lysine, cysteine, serine NH2, SH, OH-side chains, and possibly other nucleophilic groups), the resulting covalent modification can disrupt the electroactive centers responsible for the protein’s oxidation peaks

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• ”, or “proton wire” [103][104][105][106] or equivalent to balance the electron redistribution, which may explain the low activity of Cram’s model serine protease in Figure 3A [107]. Polarization was addressed by the creative “molecular clefts” of Rebek [108][109]. Although not a cavity per se, clefts

• active site (binding a substrate in an orientation that directs internally catalyzed reactivity) [347][348]. The examples of cavities with functionality discussed above, from Cram’s “full serine protease model” [87], to MOCs with flexible peripheral groups [349], to frameworks with internal proline

• reactivity. (B) Macrocycles with functional sites that react with bound substrates directly. (A) Cram’s serine protease model system [87][88]. The macrocycle showed strong substrate binding (organization), but the model did not show strong acceleration for a hydrolysis reaction. The “organized” catalytic

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• enantioselectivity is the introduction of serine-derived bisoxazoline ligands L8 (sBOX). Upon coordination with a copper catalyst, these ligands present second-sphere ester groups, which facilitate the additional stabilization of noncovalent interactions at the penta-coordinated Cu(III) intermediate 82 in the

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

• ], requires the presence of a nucleophile at the β-position of the amino acid and occurs exclusively on select amino acids. Specifically, cyclodehydration of a serine or threonine (followed by oxidation or reduction) generates an oxazole, oxazoline, or oxazolidine moiety in the NRP backbone, and the analogous

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• ]. The work by Alakpa et al. highlights how important it is to consider how one assesses the impact of co-assembly on a molecular system [20]. AFM suggested that the addition of the surfactant-like Fmoc-serine (Fmoc-S) to the fibrous Fmoc-diphenylalanine (Fmoc-FF) did not impact the structure of the Fmoc

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• and cross-coupling of different kinds of amines for approaching symmetric and unsymmetric imines [76]. This method achieved the bioconjugation of several amino acids with benzylamine, the use of phenylalanine (Phe), serine (Ser), and isoleucine (Ile) as substrates led to 85%, 59%, and 29% yield

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• glycosylation: i) N-glycosylation, where a N-acetylglucosamine (GlcNAc) is linked to the nitrogen atom of an asparagine side chain [28]; ii) O-glycosylation, where a GlcNAc or N-acetylgalactosamine (GalNAc) is linked to the hydroxy group of a serine or threonine residue [29]; iii) C-glycosylation, where a

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• work described below, KTGS was applied to multicomponent reactions in limited cases [25]. Van der Veken et al. selected as template the protein urokinase plasminogen activator, a serine protease targeted in oncology and inhibited by imidazopyridines [26]. The main challenges of this project were the

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• resulting peptides exhibit unique structural features due to thioether bridges between dehydrated serine or threonine (Dha/Dhb) and cysteine (Cys). These thioether bridges lead to cyclic peptides with the modified amino acid lanthionine (Dha-Cys) or methyllanthionine (Dhb-Cys). The strong antimicrobial

• physicochemical characteristics, number of predicted cycles (one cycle or more was required), the presence of serine (Ser) and threonine (Thr) residues, and the characteristic cleavage site of the C39 peptidases domain (GG or GA) (Table S2 in Supporting Information File 1) obtained in RiPPMiner [5]. The nine

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

• -serine, which provides the methyl group in this case. Another methyl donor that provides a C1 building block for ʟ-methionine and subsequent SAM synthesis is betaine. Betaine-homocysteine MT remethylates ʟ-homocysteine to ʟ-methionine. Non-SAM-dependent MTs catalyse B12-dependent methylations using the

• with N-terminal alanine, serine, threonine, glycine, and methionine residues, as well as the antibiotics nisin and haloduracin with good efficiency. Nisin was methylated on its N-terminal isoleucine and on the side chain of Lys12, where two methylations occurred. It is important to note that N

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• substituted saccharides. The vast diversity among CEs is organized into 16 different families [123]. Members of the CE6 family are typical serine-type esterases. A cold-adapted CE6 enzyme, CEST, was cloned and expressed in E. coli from Microbulbifer thermotolerans DAU221 with a temperature optimum of 15 °C

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• strategies to explore access to triazole–pyrazole hybrids. Triazole–pyrazole hybrids, particularly non-fused heterocycles of this class, have not been investigated systematically. Selected known derivatives (Figure 1, 1–4) inhibit the serine-threonine kinase ERK3 [12] or the cholera-causing bacterium Vibrio

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• serine (Ser), a β-hydroxyaspartic acid (Hya), and a unique γ-amino acid biosynthetically originating from an arginine and a methyl malonate (4-amino-7-guanidino-3-hydroxy-2-methylheptanoic acid), with the amino group acylated by a saturated fatty acid. Subsequent HMBC and MS/MS analyses indicated that

• , Ser: serine, Pro: proline, Orn: ornithine). (b) Validation of var biosynthetic gene cluster. The plasmid constructed for the generation of the varG null-mutant strain (varG::cmR) using the cmR gene cassette (left), and HPLC-profile comparison of the Variovorax sp. H002 wild type strain and the varG

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• , serine, and norvaline to give products 11a–f in 53–88% yields with greater than 8.5 dr (Scheme 7). The reactions with leucine and phenylglycine (R2 = iPr and Ph) as amino acids gave mainly mono-cycloaddition products and very little double cycloaddition products 11g and 11h due to the steric hindrance of