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

• , Cardiff, CF10 3AT, UK 10.3762/bjoc.22.67 Abstract Site-specific modifications of native-sequence proteins are technologies that underpin progresses in chemical biology, diagnostics and next-generation biotherapeutics. However, the pursuit of site-specificity has often come at the expense of scalability

• highlight opportunities for innovation in next-generation native-sequence protein modification technologies. Keywords: affinity-guided chemistry; disulfide-rebridging; enzyme catalysis; glycan modifications; native-sequence; protein labelling; small-molecule modifications; terminal; Introduction Protein

• -modification market is expected to reach USD 6.02 billion by 2034 (https://www.towardshealthcare.com/insights/protein-labeling-market-sizing). Review Key criteria for effective native-sequence modifications Effective protein modification relies on tools that balance three interlinked factors translating basic

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• time (τ) in IE-HPLC (Δτ = −3 min/modification, Table 1). For Ts-modified ONs, the incorporation of the Ts modifications, as a result of increased hydrophobicity, led to an increased retention time (Δτ = +1.5 to +2 min/modification, Table 1) compared to the native sequence. The composition of the ONs

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

• approach where simpler and fully synthetic intermediates of the natural product’s biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a

• 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

• synthesis of this complex natural product (Supporting Information File 1, Figure S1). Results and Discussion In order to establish the mutasynthesis of argyrins, we designed the native sequence mutasynthon 14 and various synthetic analogs of this initiating tripeptide for argyrin mutasynthesis with

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

• face of the amphipathic helical structure. All the other analogs were designed by tuning some of the physicochemical features that contribute to peptide–membrane interactions in order to preserve the activity of the native sequence. Some of these changes decreased the hemolytic activity of Dec-NH2

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• residues [16]. These analogues exhibit a decreased antifreeze activity compared to glycopeptides with the native sequence (Ala-Ala-Thr). Similar results were obtained by Peltier et al. with synthetic AFGP analogues comprising both the N-acetyl galactosamine as the carbohydrate moiety, and alanine by

• conformation with a negative band at λ ≈ 197 nm and a weak positive CD effect at about 220 nm (Figure 1), as already observed for other synthetic AFGP analogues [16][23]. However, the CD intensity is significantly lower compared to the previously published correlate 9 with the native sequence [16]. The (2S,3S