Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• –protein interactions using the tabula rasa-based particles mimicked the thermodynamics of protein–protein interactions quite well [49]. Once we were able to have proteins and nanoparticles work in harmony [50] we started working on designing systems with emergent behavior, i.e., where the particle–protein

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• substrates, i.e., this resulted in a 12-fold increase of product formation. This is an additional hint that protein–protein interactions represent an important factor in PKS systems. Further, it seemed that the carrier proteins conferred specificity for α-pyrone ring formation, since once the carrier

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

• and self-assembly processes that are crucial for cell growth and signaling. These precisely controlled association systems have been refined over billions of years of evolution. The selective recognition is driven by protein–protein interactions that operate at an interface with a surface area that is

Peptide–polymer ligands for a tandem WW-domain, an adaptive multivalent protein–protein interaction: lessons on the thermodynamic fitness of flexible ligands

• Katharina Koschek,
• Vedat Durmaz,
• Oxana Krylova,
• Marek Wieczorek,
• Shilpi Gupta,
• Martin Richter,
• Alexander Bujotzek,
• Christina Fischer,
• Rainer Haag,
• Christian Freund,
• Marcus Weber and
• Jörg Rademann

Beilstein J. Org. Chem. 2015, 11, 837–847, doi:10.3762/bjoc.11.93

• superior to induce multivalent binding and to increase affinity, while the more flexible and dendritic polymers, pHPMA and hPG are suitable to induce crosslinking upon binding. Keywords: inhibitors of protein–protein interactions; isothermal titration calorimetry; multivalency; peptide–polymer conjugates

• peptide–polymer conjugates as a chemical tool to inhibit protein–protein interactions in living cells [6]. As demonstrated for the pro-apoptotic BH3-peptides, multivalent presentation of monovalent ligand peptides can potentiate the activity of the peptide at identical overall peptide concentrations

Exploring monovalent and multivalent peptides for the inhibition of FBP21-tWW

• Lisa Maria Henning,
• Sumati Bhatia,
• Miriam Bertazzon,
• Michaela Marczynke,
• Oliver Seitz,
• Rudolf Volkmer,
• Rainer Haag and
• Christian Freund

Beilstein J. Org. Chem. 2015, 11, 701–706, doi:10.3762/bjoc.11.80

• -Universitätsmedizin Berlin, Berlin, Germany 10.3762/bjoc.11.80 Abstract The coupling of peptides to polyglycerol carriers represents an important route towards the multivalent display of protein ligands. In particular, the inhibition of low affinity intracellular protein–protein interactions can be addressed by this

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• a linear peptide sequence was accomplished using an anodic oxidation step (Scheme 21). The stabilisation of linear peptides via inducing a stabilised secondary structure is of importance in mimicking protein–protein interactions (PPI) for diseases such as cancer and HIV [89][90]. The methoxylated

Multivalent scaffolds induce galectin-3 aggregation into nanoparticles

• Candace K. Goodman,
• Mark L. Wolfenden,
• Pratima Nangia-Makker,
• Anna K. Michel,
• Avraham Raz and
• Mary J. Cloninger

Beilstein J. Org. Chem. 2014, 10, 1570–1577, doi:10.3762/bjoc.10.162

• galectin-3 binding site must then be enabling protein–protein interactions. Some of these protein–protein interactions may occur because of intertwining of the N-terminal domains that are now in close proximity. However, protein–protein interactions using the carbohydrate recognition domains of galectin-3

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

• side effects, which is considered as the greatest benefit of peptides and proteins over small molecules [7][8]. Moreover, small organic compounds are not able to address protein–protein interactions as their counterparts, the peptides/proteins [9]. Peptides share all superiorities of proteins but are

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• expression of survivin in tumors correlates with increased drug resistance, an accelerated rate of recurrence and poor patient survival [3][4]. Survivin blocks apoptosis by protein–protein interactions via its characteristic baculovirus IAP repeat domain (BIR) resulting in the formation of a complex with

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• protein–ligand or protein–protein interactions, thereby determining thermal or metabolic stabilities, which is of great importance in peptide-based drug research [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. These changes in properties may be more

A new synthetic protocol for coumarin amino acid

• Xinyi Xu,
• Xiaosong Hu and
• Jiangyun Wang

Beilstein J. Org. Chem. 2013, 9, 254–259, doi:10.3762/bjoc.9.30

• the dye BODIPY-Fl to study the dynamics of protein–protein interactions [2]. Wang and co-workers genetically incorporated 1a to a position near to amino acids, which can be phosphorylated to investigate how phosphorylation affects the fluorescence properties of 1a, and the variation in the

Peptides presenting the binding site of human CD4 for the HIV-1 envelope glycoprotein gp120

• Julia Meier,
• Kristin Kassler,
• Heinrich Sticht and
• Jutta Eichler

Beilstein J. Org. Chem. 2012, 8, 1858–1866, doi:10.3762/bjoc.8.214

• underlying the protein function. Furthermore, such mimetic molecules are promising candidates for the inhibition of protein–protein interactions. Synthetic peptides can be produced as direct reproductions of protein fragments and by diverse chemical modification, including the integration of non

• binding sites as molecular tools to explore the molecular and structural basis of protein–protein interactions. Furthermore, this strategy may be potentially useful for the structure-based design of synthetic protein-binding-site mimics by improving the conformational stability of the mimetic peptides

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• protein–protein interactions. Keywords: chemical diversity; Huisgen cycloaddition; library synthesis; peptidomimetics; solid phase synthesis; triazole; Introduction The α-helix was the first-described secondary structure of peptides discovered by Linus Pauling in 1951 [1]. With about 30% of the amino

• , but stabilization of the helix folding for small structures with less than 15 residues still remains a challenge [5][6]. Thus, new attempts have been made to design low-molecular-weight ligands that disrupt protein–protein interactions [7]. For example, fast proteolytic degradation observed with small

• potential inhibitors of protein–protein interactions. Results and Discussion Synthesis of azide-functionalized Wang resins Two azide-functionalized resins were prepared for the solid-phase synthesis of diaryl-triazoles. The commercially available 4-(bromomethyl)benzoic acid (5) was converted into azide 6 in

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

• inhibitory capacity of the lead compound GSF to block adhesion and migration both of tumor cells and vascular endothelial cells and endothelial-cell-mediated angiogenesis. Surprisingly, GSF may not only block carbohydrate–protein interactions but also integrin-mediated protein–protein interactions, and thus

• detectable carbohydrate–protein interaction, because the combined synthetic peptidic integrin ligands completely blocked cell adhesion to fibronectin, but on the other hand, cell adhesion could be inhibited with the sulfated saccharide mimetic GSF, probably by interfering with protein–protein interactions

• mediated by several different forms of integrin that adhere to either, collagen, fibronectin or laminin. Besides perturbing integrin-ECM protein–protein interactions, GSF may also interfere with ionic forces between charged ECM proteins and cells due to the negative charge of the sulfate. In order to

Investigation of the network of preferred interactions in an artificial coiled-coil association using the peptide array technique

• Raheleh Rezaei Araghi,
• Carsten C. Mahrenholz,
• Rudolf Volkmer and
• Beate Koksch

Beilstein J. Org. Chem. 2012, 8, 640–649, doi:10.3762/bjoc.8.71

• denaturation. Keywords: β- and γ-amino acids; coiled coil; foldamer; screening libraries; SPOT technique; Introduction Coiled-coil domains, which consist of two or more α-helices, are the most common representatives of α-helix-mediated protein–protein interactions, which regulate many important biological

Synthesis of fluorinated maltose derivatives for monitoring protein interaction by ¹⁹F NMR

• Michaela Braitsch,
• Hanspeter Kählig,
• Georg Kontaxis,
• Michael Fischer,
• Toshinari Kawada,
• Robert Konrat and
• Walther Schmid

Beilstein J. Org. Chem. 2012, 8, 448–455, doi:10.3762/bjoc.8.51

• interactions, is presented. This approach uses 2-F-labeled maltose as a spy ligand to indirectly probe protein–ligand or protein–protein interactions of proteins fused or tagged to the maltose-binding protein (MBP). The key feature is the simultaneous NMR observation of both 19F NMR signals of gluco/manno-type

• –ligand and protein–protein interactions [1][2]. Based on tremendous gains in sensitivity due to high-field spectrometers and cryogenic-probe technology, unprecedented structural and functional information can be obtained on biologically important protein–ligand systems and protein complexes [2]. To

• reflected in a further (proportional) increase of the line broadening (Figure 4). In a similar way, noncovalent protein–protein interactions would increase the effective molecular weight by transient binding and result in a consequently increased line width, which can be quantified to derive affinities

RAFT polymers for protein recognition

• Alan F. Tominey,
• Julia Liese,
• Sun Wei,
• Klaus Kowski,
• Thomas Schrader and
• Arno Kraft

Beilstein J. Org. Chem. 2010, 6, No. 66, doi:10.3762/bjoc.6.66

• protein enrichment and purification, sensing and diagnostics applications, as well as therapeutic uses involving interference with critical protein–protein interactions. Multivalency represents the key to generate high-affinity materials for biomacromolecules with a sufficient number of binding sites for

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

Synthesis and binding studies of two new macrocyclic receptors for the stereoselective recognition of dipeptides

• Ana Maria Castilla,
• M. Morgan Conn and
• Pablo Ballester

Beilstein J. Org. Chem. 2010, 6, No. 5, doi:10.3762/bjoc.6.5

• of protein–protein interactions is gaining interest as they are known to play a critical role in important biological processes such as the normal function of cellular/organelle structure, immune response, enzyme inhibitors, signal transduction, and apoptosis. Rational protein surface recognition

• poses a challenging test to our actual knowledge of molecular design. Nevertheless, its practice and developments will provide a better understanding of protein–protein interactions. Interestingly, in molecule-based disease therapy, the disruption of protein–protein interactions by small molecules