Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• for integrins which is critical for several diseases. Keywords: biphenyltetracarboxylic acid; homo-coupling; integrin inhibitor; rhodium catalyst; Ullmann-type reaction; Introduction The Ullmann reaction is a coupling reaction of aryl halides using copper, traditionally using metallic copper-bronze

• Integrins are transmembrane heterodimers, each consisting of α and β subunits, that mediate cell–cell and cell–matrix adhesion involved in normal and pathological processes. Bidirectional signaling through integrins regulate cell shape, motility, and cell cycle progression [23]. The integrin complexes are

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• -linked glycans on the cell surface. Surface proteins such as integrins [6][7], vascular endothelial growth factor receptor [8], and lysosome-associated membrane proteins [9] are known to be crosslinked by galectins, giving galectins a modulating role in cell adhesion, blood vessel growth and cellular

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• increased expression by 9 and 11 fold, respectively, was obtained when endothelial cells were treated with C4HSL (Figure 5). Migration of leukocytes from vessels into infected tissues involves interaction with endothelium through adhesion molecules. Adhesion molecules such as integrins (Cd11/Cd18) and ICAMs

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• integrins. However, the possible H-bonding interactions between neighboring RGD units could be a drawback in view of the accessibility of the arginine groups to interact with the integrins. Photophysical properties of RuII-calixarene conjugate 9 The absorption and emission spectra of Ru-calix(RGD)4

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• yield, whereas the treatment with 42% aq HBF4 of the compounds 65 and 66 regenerated 61+.BF4− in good yields. Integrins are transmembrane α/β heterodimers that bind to extracellular matrix ligands, cell-surface ligands, and soluble ligands [72]. Perron-Sierra’s group prepared substituted benzo[7

• αvβ5 integrins. Benzo[7]annulenylidenes 73–75 and their rearrangements have attracted much interest due to their thermal and photochemical transformations (Figure 5) [74][75][76]. For the first time, Jones reported the chemical trapping of thermal and photochemical decomposition of the tosylhydrazone

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

• ]. The RGD motif is contained in various proteins like fibrinogen, fibronectin, prothrombin, tenascin and other glycoproteins [43] and is known to be recognized by over 10 integrins, among the over 24 known integrins [44][45], including all αv integrins, α5β1, α8β1 and αIIbβ3 [46]. The fact that

• carcinogenesis is highly dependent on migration, invasion and angiogenesis renders integrins important anticancer targets. Integrin αvβ3 is an important factor in tumor angiogenesis and metastasis [45], two common characteristics of cancer that discriminates it from other diseases. Notably, integrin αvβ3 (also

• known as the vitronectin receptor) appears to be the most important among all integrins regarding cell proliferation, invasion and angiogenesis [47]. This integrin is overexpressed on activated endothelial cells, new-born vessels and other tumor cells [48][49], but it is found to be expressed at

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• different integrins (RGD, collagen, etc) next to CD13 receptor [20]. HT-29 expresses all the known β1 RGD dependent receptors furthermore αvβ3, αvβ5, αvβ6, αvβ8 [21]. Most of the mentioned integrins bind isoDGR peptides with different affinity from nM up to μM concentration that depends on the structure of

• the peptide [2]. In addition the binding affinity of the different integrins is not consequent to the peptides. Furthermore, there are only a few binding affinity studies for CD13 suggesting several hundred nM IC50 values for NGR peptide derivatives [22]. The biological activity of NGR and isoDGR

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

• +, α5β1−) cells in the presence of excess cilengitide, with the aim of blocking integrins on the cell surface. Using the MDA-MB-468 cell line, a fivefold increase of the IC50 was observed for the conjugates in the presence of excess cilengitide, which is known to strongly bind not only αVβ3, but also αVβ5

• , αVβ6, and α5β1. These data indicate that in this case the cyclo[DKP-isoDGR]-α-amanitin conjugates are possibly internalized by a process mediated by integrins different from αVβ3 (e.g., αVβ5). Keywords: antitumor agents; cancer; drug delivery; integrins; peptidomimetics; Introduction α-Amanitin is a

• [40] were carried out in which conjugates 10 and 11 were tested on U87 (αVβ3+, αVβ5+, αVβ6−, α5β1+) [34][35][36] and on MDA-MB-468 (αVβ3−, αVβ5+, αVβ6+, α5β1−) [34][35][36] cells in the presence of 50-fold excess of cilengitide [23], with the aim of blocking integrins on the cell surface (Table 4, see

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• ) [19][20], pulmonary surfactant-associated protein D (SP-D) [21], dendritic cell-specific ICAM-3-grabbing non-integrins 1 and 2 (DC-SIGN, also known as CD209; and DC-SIGNR, also known as CD299) [22][23], and mannose-binding protein (MBP) [24]. These CLECs exert their function through different

Regulation of integrin and growth factor signaling in biomaterials for osteodifferentiation

• Qiang Wei,
• Theresa L. M. Pohl,
• Anja Seckinger,
• Joachim P. Spatz and
• Elisabetta A. Cavalcanti-Adam

Beilstein J. Org. Chem. 2015, 11, 773–783, doi:10.3762/bjoc.11.87

• differentiation. It has been shown that integrins exert an extensive crosstalk with many growth factor receptors [16]. Integrin ligands actively participate in the regulation of growth factor-mediated signaling. Ligand–integrin interactions can induce ligand-independent partial activation of growth factor

• receptors and result in optimal cell survival and migration signals. Growth factor-mediated activation of the receptors leads to clustering of integrins and activation of integrin signaling [8][17]. In a word, the crosstalk between integrins and growth factor receptors is bidirectional that integrins may

• signaling of integrins and growth factor receptors are discussed. Integrin ligands for cell adhesion and stem cell fate In order to enhance the effectiveness of cell-based bone therapy, it is important to understand the signals from integrin–ligand interactions. New technologies have been employed to

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• , the tumor cells express pro-angiogenic factors including growth factors such as the vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and enzymes such as cyclooxygenase 2 (COX-2) and protein kinase A (PKA) as well as signaling molecules such as integrins. The evoked cascade

Synthesis of novel conjugates of a saccharide, amino acids, nucleobase and the evaluation of their cell compatibility

• Dan Yuan,
• Xuewen Du,
• Junfeng Shi,
• Ning Zhou,
• Abdulgader Ahmed Baoum and
• Bing Xu

Beilstein J. Org. Chem. 2014, 10, 2406–2413, doi:10.3762/bjoc.10.250

• exploration [26]. As an amino acid, Phe or naphthAla increases molecular aromatic–aromatic interactions [19][21][27]. Arg-Gly-Asp, which is a well-established tripeptidic epitope, that modulates mammalian cell adhesion through binding with integrins on the cell membrane [28][29]. Thymine or adenine, as a

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• grow ECs on TPX membranes. We found that this new TPX membrane 8a showed reduced biological potency to bind ECs. This observation is in accordance with studies by Beer et al. who showed that virtually all RGD binding sites can be reached by integrins, when the distance between the surface and the RGD

• peptide amounts to 46 Å. Access by integrins again decreases when the spacer is longer and likely folds in such a way that RGDs become less surface-exposed [34]. Conclusion In conclusion we developed a protocol for functionalizing polyhydrocarbons, here poly(4-methylpent-1-ene) (TPX), which are important

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

• Grazia Marano,
• Claas Gronewold,
• Martin Frank,
• Anette Merling,
• Christian Kliem,
• Sandra Sauer,
• Manfred Wiessler,
• Eva Frei and
• Reinhard Schwartz-Albiez

Beilstein J. Org. Chem. 2012, 8, 787–803, doi:10.3762/bjoc.8.89

• , which are important for their metastatic property, have been intensely investigated. Among these, integrins, which are hetero-dimeric integral membrane proteins, are involved in protein–protein mediated adhesion of cells to the extracellular matrix (ECM). Aberrant levels of several integrins have been

• observed in malignant melanomas. While some integrins such as α6β1 and αvβ5 are down-regulated, others such as αvβ3, α4β1 and α3β1 are up-regulated [3]. Integrins bind to ECM-proteins and this constitutes the strongest interaction in the adhesion processes. The importance of the fibrinogen receptor αvβ3 in

• with the ECM. To characterize the affected interactions in more detail, cells were incubated with peptidic integrin ligands and GSF in combination. The RGD motif (an arginine–glycine–aspartic acid peptide sequence) is recognized and bound by several integrins including αvβ3 and α5β1. The sequence

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32