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

• specifically recognizes and binds to surface antigens present on tumor or other targeted cells. (2) Linker: the linker connects the antibody to the payload. The nature of the moiety linking the drug/radiolabel/imaging agent to the antibody plays a crucial role in the pharmacokinetic properties [4][5

• trodelvy, used in a treatment for patients with triple-negative breast cancer, the linker may release the drug prior to internalization. (3) Payload: The payload may be a subunit used in cellular tracking, imaging, or most commonly toxic drug therapeutics. The overall goal of ADCs is to deliver the payload

• antibodies [11]. In the case of ADCs, conjugation of the linker/payload to the antibody must not drastically alter the pharmacokinetics or physicochemical properties of the antibody [12][13]. Typically, zero to eight payloads are attached to the antibody. Heterogeneous ADCs may thus be a mix of both

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• particularly effective against multidrug-resistant cancers. Keywords: cancer treatment; cryptophycins; drug conjugates; payload; targeted delivery; Introduction Cryptophycins emerged as highly potent cytotoxins for the use in targeted cancer therapy [1]. Originally discovered over three decades ago by

• cryptophycin-1, failed in clinical studies as a cytotoxic drug on its own due to severe side effects [4]. However, the embedment of cryptophycins as payloads in drug conjugates, increases specificity and minimises adverse effects [5][6]. Drug conjugates usually consist of three units, where the payload is

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

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

• organ and protect the payload during the passage through physiological barriers. Most importantly, pH-sensitive DDS are considered as suitable carriers for chemotherapeutics [44][45][46]. Furthermore, peptides also play an important role as active moieties for many diseases, including cancer [47

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

• activation, Y1 receptor-mediated PDC internalization, as well as the payload liberation, of this type of peptide–toxin conjugate. Due to the structural identity of the used peptide moieties, we suppose a similar Y1 receptor binding and activation behavior for the tubugi-1 bearing PDC described herein, albeit

• affinity and specificity as well as metabolic stability of the peptide moiety, and to identify novel PDC payloads permitting superior PDC efficacies. Even with a good targeting peptide at hand, many other constrains apply to achieve a good conjugate drug: (1) the toxin (warhead, payload) must be highly

• active, as normal activity (medium to high nM IC50 like in taxanes or epothilones) [41][42][43] often is insufficient considering common receptor densities; (2) the linker must be designed to either not negatively affect activity of the payload, or even better to preclude activity in non-activated

Novel unit B cryptophycin analogues as payloads for targeted therapy

• Eduard Figueras,
• Adina Borbély,
• Mohamed Ismail,
• Marcel Frese and
• Norbert Sewald

Beilstein J. Org. Chem. 2018, 14, 1281–1286, doi:10.3762/bjoc.14.109

• activity of specific enzymes. The connection between the payload and the linker is of crucial importance since its stability can dramatically change the release and thus, the activity of the compound. For this reason, the included functional groups were designed with the consideration to provide

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• conjugation with the therapeutic payload. The overall experimental procedure to synthesize a PDC is usually rapid and facile. Notably, the overall cost to produce a PDC, where an already approved drug can be selected and re-used from a pool of available cytotoxic agents, is much lower compared to the cost of

• order to efficiently reach the malignant tumor site and release the payload in its microenvironment, reducing the off-target toxicity. The cytotoxic agent should contain proper functional group that can be linked to the tumor homing peptide (i.e., gemcitabine [19]) or if it is not present it should be

Synthesis and biological evaluation of RGD and isoDGR peptidomimetic-α-amanitin conjugates for tumor-targeting

• Lizeth Bodero,
• Paula López Rivas,
• Barbara Korsak,
• Torsten Hechler,
• Andreas Pahl,
• Christoph Müller,
• Daniela Arosio,
• Luca Pignataro,
• Cesare Gennari and
• Umberto Piarulli

Beilstein J. Org. Chem. 2018, 14, 407–415, doi:10.3762/bjoc.14.29

• hepatocytes, where the transporting protein OATP1B3 internalizes amatoxins resulting in high liver toxicity [2][3]. This strong toxicity in the presence of endocytosis mediators allowing cell permeation, aroused interest towards the use of α-amanitin as a payload for targeted cancer therapy. In 1981, Davis

Smart molecules for imaging, sensing and health (SMITH)

• Bradley D. Smith

Beilstein J. Org. Chem. 2015, 11, 2540–2548, doi:10.3762/bjoc.11.274

• producing reactive singlet oxygen [41][42][43]. The dyes enable new types of nanoscale heating technologies that release sensitive payload such as dyes, drugs, oligonucleotides, or proteins. The dyes can also be loaded into nanoparticles for anticancer photothermal therapy in preclinical animal models

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• Permeation and Retention) effect [20], and the ability to carry increased payload, compared to natural CDs. Only few examples of CD oligomers have been studied as hosts to drugs [21]. On a practical point of view, on the other hand, not many reactions have been efficiently applied to produce CD oligomers