Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• functionalized nature of polypeptides/proteins demands exquisite selectivity to target specific sites on the macromolecule of interest. In addition to the requisite features of the chemical methods outlined above, there are key requirements for synthetic methods used in ADCs, which include high site-selectivity

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• debate has prompted exploration into novel materials that resemble PEG, retaining its positive attributes, but add biodegradability. Two of such classes of polymers that would form viable alternatives are polyoxazolines and polypeptides [10][11], both of which possess biodegradable and biocompatible

• for the use in drug delivery systems [12]. In this regard, synthetic polypeptides emerge as a promising candidate for constructing biodegradable and biocompatible polymersomes. Leveraging the inherent presence of peptide-degrading mechanisms within the human body and the versatile chemical

• functionalities of naturally occurring amino acids, synthetic polypeptides offer a robust platform for designing drug delivery systems that meet the criteria of biodegradability and biocompatibility [13]. The present study focuses on a polysarcosine and poly-ʟ-(benzyl glutamate) block copolymer (PSar-PBLG), as it

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

• )–H functionalization C–N coupling reaction by developing an electrochemical method for the bioconjugation of tyrosine in proteins/polypeptides with phenothiazine residues, achieving excellent site- and chemoselectivity (Scheme 4a). This method was inspired by an earlier work from the Gouin group

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• heterologous hosts. Xie et al. introduced a multigene expression vector (GjCCD4a-GjALDH2C3-GjUGT74F8-GjUGT94E13) into N. benthamiana by using the fusion and 2A polypeptides strategy and obtained a crocin yield of 78,362 ng/g (fresh weight). The content of crocin-I (2a) and crocin-II (2b) accounted for 99% of

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

• cis and trans isomers compared to isolated NMA. The presence of diastereomers in the peptide bonds is less likely since the cis/trans ratio in polypeptides is lower than 1:820 (i.e., an energy difference greater than 4.0 kcal mol−1 in favour of the trans isomer) [84]. It is, however, currently

• shown to be a highly effective tool to sample the conformational space of polypeptides made of sequences of 10 to 30 amino acids [87][88] and of macrocycles [89]. Our simulation strategy, mainly adapted from the latter references, made use of 15 independent 700 ns-long aMD simulation runs for each

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

• achieved by solid-state synthesis. Our synthetic strategy could synthesize the target peptide in high yield with good purity Keywords: antimalarial; highly methylated polypeptides; hoshinoamides; total synthesis; Introduction Malaria is an insect-borne infectious disease caused by parasites of the genus

• of the malaria parasites (IC50 = 0.96 μM) and African sleeping sickness (IC50 = 2.9 μM). Hoshinoamide C was firstly synthesized from Boc-protected amino acids in liquid phase [12]. Both hoshinoamides A and B are highly methylated polypeptides containing three N-methyl amino acids: N-Me-ʟ-Leu7, N-Me-ᴅ

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• concentration of the polymer, but also by the nature of the anion as well as its concentration. Moreover, UCST behavior induced by BF4− was also detected in aqueous solutions of polypeptides, whose side chains contain charged pyridinium or imidazolium functionalities [290][291]. In contrast to single charged

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• methionine aminopeptidase type-2 (MetAP-2) enzyme [129]. MetAP-2 is involved in cell proliferation, translation and post-translational modifications of nascent polypeptides and is therefore essential for cell viability [130][131]. Additionally, fumagillin is also known to be overproduced upon caspofungin

Synthetic accesses to biguanide compounds

• Oleksandr Grytsai,
• Cyril Ronco and
• Rachid Benhida

Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82

• polypeptides, obtained the same compound, produced by an undesired concomitant self-condensation of the N-amidinopyrazole reagent. This transformation was further investigated in the preparation of N-amidino-amidinopyrazole hydrochloride from N-amidinopyrazole in DMF with DIPEA at room temperature in a

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

• Marek Kõllo,
• Marje Kasari,
• Villu Kasari,
• Tõnis Pehk,
• Ivar Järving,
• Margus Lopp,
• Arvi Jõers and
• Tõnis Kanger

Beilstein J. Org. Chem. 2021, 17, 581–588, doi:10.3762/bjoc.17.52

• polypeptides: KshA (terminal oxygenase) and KshB (ferredoxin reductase). When expressed together in E. coli, active KSH is formed, and several steroids can be oxidized in the C9 position [29][30]. Out of five KshA homologues found in R. rhodochrous, only KshA5 is able to utilize C11-hydroxylated cortisone, 11β

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

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• demonstrate the enormous influence of branching on the overall yield yoa and synthesis efficiency Effsyn. Fragment strategy: fragment linking in peptides synthesis In synthetic peptide chemistry, amino acids are sequentially built up to form long oligo/polypeptides. For reasons of transparency, we have

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• organic anion transporting polypeptides (OATP) protein family [3][4]. Human OATP2B1 is one of the OATPs transporting estrone 3-sulfate, expressed in the intestine, blood–brain barrier, liver and placenta [5][6][7][8][9]. Moreover, OATP2B1 is overexpressed in certain malignancies, including breast cancer

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• that, in addition to antimicrobial resistance, forms biofilms, a complex matrix of extracellular polysaccharides, polypeptides and DNA, which act as an additional protective barrier [30]. P. aeruginosa employs two lectins for biofilm formation and host–cell adhesion: proteins LecA and LecB [31][32

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• ]. Dubinskaya reviewed early investigations into the grinding and stretching of polypeptides and proteins which showed rapid loss of enzyme activity at 80 K [101]. In contrast, more recent reports, in which both native and immobilised enzymes were ground at higher temperatures, demonstrated efficient

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• development of peptide-based contrast agents for 19F imaging [22]. In polypeptides, the incorporation of fluorine can significantly alter the properties of the native molecule. The hydrophobicity [23][24], conformational equilibria [25], and the thermodynamic [26][27][28][29] and kinetic [30][31] folding

• polypeptides is still not fully understood and it may appear controversial in the literature. For example, a donor–acceptor type enhancement of the face-to-face stacking of phenyl- and pentafluorophenyl groups has been suggested [36]; though, subsequent studies of α-helical [37], peptoid [38], and collagen

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

• were obtained with human dermal microvascular endothelial cells (HDMVEC), murine L929 fibroblasts and HeLa cells. Mechanistic studies in a cell-free system then showed that mycolactone efficiently inhibited the co-translational translocation of polypeptides into the ER, while the post-translational

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• nanoparticles has enabled photomodulation of nanoparticle fluorescence [10][11]. Similarly, tagged N-alkylcarboxyspiropyrans have provided the basis for photoactive biopolymers, e.g., polypeptides with photocontrolled folding [12], light-activated enzymes [13], light-enhanced affinity chromatography using

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

• harbor the catalytic domains on large polypeptides that can exceed sizes of one MDa [2]. PK compounds are assembled either in a linear manner, where multiple modules successively condense precursor units to the final compound (modular systems) [3], or in a recursive manner, with the catalytic domains of

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• peptides and oligopeptides under prebiotic conditions. However, initially only very short peptides were produced in experiments under such conditions, raising doubts over their potential role as a precursor of life. When forming α-helices however, longer polypeptides can be stabilized by the formation of

• enhanced by electrostatic interactions between amino acids residing on the c and g positions of the α-helices. Ghadiri et al. showed that such coiled-coil peptides are capable of self-replication [35]. As depicted in Figure 7, helical polypeptides can act as a template for shorter peptide fragments by

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

• that they split, fuse, get internalised and make complex internal networks [15]. Beside lipids, polypeptides form coacervates, which also allow for compartmentalisation [16]. A main difficulty to understand the process is that membrane proteins must fold within two-dimensional (2D) bilayers. This

• -degradation (proteolysis). Interestingly, rather than working against the ubiquitous presence of polypeptides during early steps of metabolism, this activity opened up a complementary function, that of resisting proteolysis. This created an essential selective step that enriched metabolic pathways with a

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• acceptors for PEG-sialic acid (Scheme 2). This technique was applied to polypeptides used clinically and has the advantage that it is easier to produce a recombinant protein using E. coli than to obtain the glycosylated forms in eukaryotic cells [31]. Chemical glycation of a protein and PEGylation after

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• polypeptides being commercially produced by recombinant expression [10]. In general, the quality of chemically synthesized peptide therapeutics is comparable to recombinantly or enzymatically produced compounds. The success story of SPPS, which has been going on for 50 years now, has shown that these molecules

• conventional strategy for peptide PEGylation is the use of the SPPS technique. Here, polypeptides with specifically protected side chains are synthesized by automated SPPS according to the strategy that is applied for the introduction of fatty acids. Following deprotection of the desired side chain, this can

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• (tosylate) → –N3) in the PG layer, and click conjugation of the basic polypeptides (Arg8, Lys8 or His8) terminated with propargyl glycine. The ND-PG-BPP exhibited good dispersibility in water (>1.0 mg/mL) and positive zeta potential ranging from +14.2 mV to +44.1 mV at neutral pH in Milli-Q water. It was

• ; polyglycerol; polypeptides; Introduction A variety of nanoparticles have been investigated as nonviral vectors in drug and gene delivery systems [1][2]. Among these nanoparticles, nanodiamond (ND) has attracted a great deal of attention due to its high chemical stability, low toxicity, and large specific

• case of ND, for example, basic polypeptides [16], polyamine polymer [17], primary and tertiary amines [17][18], and quaternary ammonium salts [19] were employed to coat ND covalently or noncovalently as positively charged ligands for DNA immobilization. Although the functionalized ND is proven to