Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• ] promotes the binding of ligands exhibiting a high local negative charge density, such as sulfotyrosinated P-selectin glycoprotein ligand-1 (PSGL-1) [23] or heparin [24]. A versatile synthetic ligand that takes advantage of binding to cationic target sites, is dendritic polyglycerol sulfate [25] (dPGS), due

• 250 nM which is 20-fold lower compared to the unfunctionalized tetra(ethylene glycol)-decorated supramolecular polymers I (IC50 = 5 µM). Further, the affinity is significantly higher compared to naturally binding unfractionated heparin (15 kDa, IC50 = 12 µM) or artificial polyglycerol sulfate of

• similar molecular weight and number of sulfate groups (dPG3kDaS11: IC50 = 17 µM; dPG6kDaS8: IC50 = 50 µM) [26]. However, the densely sulfated dendritic polyglycerol of similar molecular weight is able to bind in the low nanomolar range suggesting that a high density of functional groups is a key parameter

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• and a high electrochemical response [74]. CuAAC has been successfully used to immobilize molecules on polymers and biopolymers as well as to join sugars to peptides and proteins. CD-polyglycerol dendron amphiphiles (CD-PG) have also been obtained. This derivative showed high encapsulation efficiency

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 dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• with low dispersity. Moreover, the tree-like structure of such polymers provides multivalent positions for functionalization and interaction with DNA/siRNA. Dendritic polyglycerol (dPG) can be synthesized on a kilogram scale by a one-step, ring-opening polymerization of glycidol with controllable sizes

• according to a published procedure [33]. Fifty percent of all (~110) hydroxy groups on dendritic polyglycerol were functionalized with amino groups in a three-step protocol [27]. Briefly, the transformation was started with the mesylation of the hydroxy groups on dPG. In the next step, the mesylated

• polyglycerol was converted to polyglycerolazide. In the last step, azide functionalities (N3) were reduced to primary amines (-NH2) via Staudinger reduction (Scheme S1 in Supporting Information File 1). For coupling both amino acids Arg and His to the dendritic backbone, a solution of dPG-NH2, 30 mg (0.20 mmol

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

• properties. Hyperbranched polymers like polytriallylsilane or polyglycerol have been used in a wide range of transformations including aldol condensations [22], Suzuki cross-couplings [23] and Diels–Alder reactions [24], to name a few, with metal complexes as catalytically active principle. The advent of

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

• 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

• which demonstrates that the new carrier provides a venue for the future inhibition of proline-rich sequence recognition by FBP21 during assembly of the spliceosome. Keywords: FBP21-tWW; isothermal titration calorimetry; multivalent polymers; polyglycerol peptide conjugates; proline-rich sequence

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• vector consisting of nanodiamond, polyglycerol, and basic polypeptide (ND-PG-BPP) has been designed, synthesized, and characterized. The ND-PG-BPP was synthesized by PG functionalization of ND through ring-opening polymerization of glycidol on the ND surface, multistep organic transformations (–OH → –OTs

• ; polyglycerol; polypeptides; Introduction A variety of nanoparticles have been investigated as nonviral vectors in drug and gene delivery systems [1][2]. Among these nanoparticles, nanodiamond (ND) has attracted a great deal of attention due to its high chemical stability, low toxicity, and large specific

• , which is covered with organic functional groups [12]. Quite recently, we found that ring-opening polymerization of glycidol is initiated at the oxygen-containing functionalities, hydroxy and carboxy groups, on the ND surface to give polyglycerol- (PG) grafted ND with 30 nm size (ND30-PG) [13]. 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

• compared to the homopolymer PGA should lead to simplified processing conditions. The findings contribute to broadening the range of biomedical applications of PGA. Keywords: block copolymer; hyperbranched; PGA; polyester; polyglycerol; poly(glycolide); star polymer; Introduction Linear aliphatic

• 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

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• dendritic polyglycerol supported Mn-salen catalyst 50, was recently developed in a continuous membrane flow reactor [53]. This type of flow system involves the continuous removal of the product from the high molecular weight macrostructured catalysts by filtration through a nanomembrane (Scheme 14). In this