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

• Informationstechnik Berlin, Numerical Analysis and Modelling, Takustr. 7, 14195 Berlin, Germany 10.3762/bjoc.11.93 Abstract Three polymers, poly(N-(2-hydroxypropyl)methacrylamide) (pHPMA), hyperbranched polyglycerol (hPG), and dextran were investigated as carriers for multivalent ligands targeting the adaptive

• peptide–polymer conjugates pHPMA-1 and pHPMA-2 via native chemical ligation with the N-cysteinylated peptide CGPPPRGPPPR-NH2 (P2). In contrast, the second carrier molecule, hyperbranched polyglycerol (hPG) was selected as a dendritic polymer. While the backbone of PG is relatively flexible by itself, the

• biocompatible polymers, namely linear poly(N-2-hydroxypropyl)methacrylamide (pHPMA), hyperbranched polyglycerol (hPG), and linear 2-carboxyethyldextran are suited for the construction of peptide–polymer conjugates, which can be used as potent multivalent ligands for a flexible protein–protein interaction site

Adsorption mechanism and valency of catechol-functionalized hyperbranched polyglycerols

• Stefanie Krysiak,
• Qiang Wei,
• Klaus Rischka,
• Andreas Hartwig,
• Rainer Haag and
• Thorsten Hugel

Beilstein J. Org. Chem. 2015, 11, 828–836, doi:10.3762/bjoc.11.92

• hyperbranched polyglycerol as a hydrophilic core with numerous DOPA (catechol) groups attached. A similar system has already proven to be advantageous for an antifouling coating on titanium oxide surfaces [21][22]. An added benefit of this system is that the oxidation of catechol to quinones makes crosslinking

• catechol on hPG. Conclusion The desorption of different catechol-functionalized hyperbranched polyglycerol molecules from a titanium dioxide surface can lead to very high forces and a reversible bond formation. We described several parameters necessary to obtain reliable, high monovalent desorption forces

• up/lying down” mechanism [25] or even more likely via “rolling” into minima of the free energy [26]. We anticipate that these results will help improve catecholic hPGs as stable surface coatings in aqueous buffer [22]. Experimental hPGs Hyperbranched polyglycerol (hPG) with Mn ≈5000 g/mol and Mw

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• described. A modified tyrosine-based imidazolidin-4-one was grafted to a soluble high-loading hyperbranched polyglycerol via a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction and readily purified by dialysis. The efficiency of differently functionalized multivalent organocatalysts 4a–c was

• loss of activity due to immobilization, albeit moderate enantioselectivities were observed. Moreover, easy recovery by selective precipitation allowed the reuse of the catalyst for three cycles. Keywords: Friedel–Crafts; homogeneous catalysis; hyperbranched polyglycerol; imidazolidin-4-one

• decided to use hyperbranched polyglycerol (hPG) [49] as a polymeric support. The high local concentration of hydrophilic functionality present on its periphery is especially attractive since it might promote water coordination. These properties prompted us to investigate the effects of high-loading

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

• individual WW domains and with a KD of 150 μM to the tandem-WW1–WW2 construct. Secondly, this sequence was coupled to a hyperbranched polyglycerol (hPG) that allowed for the multivalent display on the surface of the dendritic polymer. This novel multifunctional hPG-peptide conjugate displayed a KD of 17.6 µM

• ligands for a target protein. The hyperbranched polyglycerol amine (hPG-NH2) with different degrees of amine functionalization can easily be prepared from hPG-OH with high yields in three steps, as reported in the literature [15]. It can be used for peptide coupling, while it is still maintaining the

Cyclodextrin-induced host–guest effects of classically prepared poly(NIPAM) bearing azo-dye end groups

• Gero Maatz,
• Arkadius Maciollek and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 1929–1935, doi:10.3762/bjoc.8.224

• observed. Additionally, this azo-dye-end-group-labeled polymer was complexed with hyperbranched polyglycerol (HPG) decorated with β-CD to generate hedgehog-like superstructures. Keywords: azo-dye; cyclodextrins; end-group functionalization; host–guest interaction; supramolecular aggregation; Introduction

• strong evidence for the interaction between the hydrophobic azo-dye end group and the hydrophilic RAMEB-CD ring. Based on this experience, the complexation of the azo-dye end group of 6 with hyperbranched polyglycerol (HPG, 7) decorated with β-CD was investigated. This kind of supramolecular structure

• , we were able to show the formation of a hedgehog-like superstructure, based on a hyperbranched polyglycerol, bearing CD moieties, and the end-group-modified PNIPAM 6. Experimental General remarks All reagents used were commercially available (Sigma-Aldrich, Acros Organics) and used without further

Poly(glycolide) multi-arm star polymers: Improved solubility via limited arm length

• Florian K. Wolf,
• Anna M. Fischer and
• Holger Frey

Beilstein J. Org. Chem. 2010, 6, No. 67, doi:10.3762/bjoc.6.67

• which significantly exceed the molecular weight of processable oligomeric linear PGA (<1000 g/mol). This was achieved by the use of a multifunctional hyperbranched polyglycerol (PG) macroinitiator and the tin(II)-2-ethylhexanoate catalyzed ring-opening polymerization of glycolide in the melt. With this

• from dendrimers [17][18], well-defined hyperbranched polymers [19] fulfill this requirement and benefit from their accessibility via a facile one-step synthesis, which makes a tedious, generation-wise build-up ubiquitous. Besides poly(ethylene imine) (PEI) [20], hyperbranched polyglycerol [21][22][23

• received. The synthesis of hb-PG was conducted as described in previous publications, using the slow monomer addition technique [21][25][26]. “Grafting from” polymerization of glycolide with hyperbranched polyglycerol-polyol as a macroinitiator. In a typical experiment, exemplified for the synthesis of