<p>List of Contributors xi</p> <p>Foreword xv</p> <p>Preface xvii</p> <p><b>Part I General Introduction to Multivalent Interactions 1</b></p> <p><b>1 Additivity of Energy Contributions in Multivalent Complexes 3<br /></b><i>Hans?-Jorg Schneider</i></p> <p>1.1 Introduction 3</p> <p>1.2 Additivity of Single Interactions – Examples 3</p> <p>1.3 Limitations of Additivity 7</p> <p>1.3.1 Free Energy Values ΔG Instead of Enthalpic and Entropic Values ΔH, TΔS 7</p> <p>1.3.2 Mismatch as Limitation of Additivity 9</p> <p>1.3.3 Medium Effects as Limiting Factor 12</p> <p>1.3.4 Strain and Induced Fit 12</p> <p>1.4 Cooperativity 13</p> <p>1.5 Allostery 14</p> <p>1.6 Conclusions 17</p> <p>References 18</p> <p><b>2 Models and Methods in Multivalent Systems 23<br /></b><i>Jurriaan Huskens</i></p> <p>2.1 Introduction 23</p> <p>2.1.1 General Introduction 23</p> <p>2.1.2 Multivalent versus Cooperative Interactions 24</p> <p>2.2 Numerical Data Analysis 25</p> <p>2.2.1 Model Simulations Using a Spreadsheet Approach 26</p> <p>2.2.2 Setting Up and Assessing Titrations 30</p> <p>2.2.3 Using Spreadsheet Simulations to Fit Experimental Data to a Model 36</p> <p>2.3 Models for Multivalent Systems 41</p> <p>2.3.1 The Simplest Multivalent System: A 1:1 Complex with Two Interaction Sites 41</p> <p>2.3.2 Multivalent Binding at Surfaces 46</p> <p>2.4 Special Multivalent Systems 53</p> <p>2.4.1 Increasing the Valency of Interfacial Assemblies: Dendrimers, Oligomers, and Polymers 53</p> <p>2.4.2 Heterotropic Interactions 58</p> <p>2.4.3 Kinetics and Dynamics 63</p> <p>2.5 Conclusions 68</p> <p>Acknowledgments 68</p> <p>References 68</p> <p><b>3 Design Principles for Super Selectivity using Multivalent Interactions 75<br /></b><i>Tine Curk, Jure Dobnikar, and Daan Frenkel</i></p> <p>3.1 Introduction 75</p> <p>3.1.1 Background: Ultra?-sensitive Response 75</p> <p>3.2 Super Selectivity: An Emergent Property of Multivalency 78</p> <p>3.3 Multivalent Polymer Adsorption 84</p> <p>3.4 Which Systems are Super Selective? 86</p> <p>3.4.1 Rigid Geometry Interactions 86</p> <p>3.4.2 Disordered Multivalency 87</p> <p>3.5 Design Principles for Super?-Selective Targeting 90</p> <p>3.6 Summary: It is interesting, but is it useful? 93</p> <p>Appendix 3.A: What Is Effective Molarity? 95</p> <p>Acknowledgements 98</p> <p>References 98</p> <p><b>4 Multivalency in Biosystems 103<br /></b><i>Jens Dernedde</i></p> <p>4.1 Introduction 103</p> <p>4.2 Cell–Cell Adhesion 104</p> <p>4.2.1 Homotypic Interactions, Cadherins Keep Cells Together 105</p> <p>4.2.2 Selectins, Heterotypic Cell Adhesion to Fight Infections 106</p> <p>4.2.3 Bacterial Adhesion by FimH 108</p> <p>4.3 Phase Transition, Multivalent Intracellular Assemblies 109</p> <p>4.4 Multivalency in the Fluid Phase, Pathogen Opsonization 111</p> <p>4.5 Conclusion 113</p> <p>Acknowledgment 113</p> <p>References 114</p> <p><b>Part II Multivalent Systems in Chemistry 121</b></p> <p><b>5 Multivalency in Cyclodextrin/Polymer Systems 123<br /></b><i>Akihito Hashidzume and Akira Harada</i></p> <p>5.1 Introduction 123</p> <p>5.2 General Perspectives of Multivalency in Cyclodextrin/Polymer Systems 125</p> <p>5.3 Typical Examples of Multivalency in Cyclodextrin/Polymer Systems 126</p> <p>5.3.1 Formation of Polymer Aggregates from Cyclodextrin?-Polymers and Guest?-Polymers 126</p> <p>5.3.2 Selectivity of Interaction Enhanced by Multivalency 127</p> <p>5.3.3 Self?-Healable Hydrogels Based on Multivalency 134</p> <p>5.4 Summary and Outlook 136</p> <p>Acknowledgments 136</p> <p>References 138</p> <p><b>6 Cucurbit[n-uril?-Mediated Multiple Interactions 143<br /></b><i>Zehuan Huang and Xi Zhang</i></p> <p>6.1 Introduction to Cucurbit[n-uril Chemistry 143</p> <p>6.2 Heteroternary Complexes 143</p> <p>6.3 Homoternary Complexes 146</p> <p>6.4 Conclusions 150</p> <p>References 150</p> <p><b>7 Multivalency as a Design Criterion in Catalyst Development 153<br /></b><i>Paolo Scrimin, Maria A. Cardona, Carlos M. Leon Prieto, and Leonard J. Prins</i></p> <p>7.1 Introduction 153</p> <p>7.2 Formation of Enzyme?-Like Catalytic Pockets 154</p> <p>7.3 Cooperativity Between Functional Groups 157</p> <p>7.4 Mechanistic Effects 161</p> <p>7.5 The Dendritic Effect in Multivalent Nanozymes 164</p> <p>7.5.1 Peptide?-Based Dendrimers for the Cleavage of Phosphodiesters 166</p> <p>7.5.2 Catalytic 3D SAMs on Au NPs 168</p> <p>7.6 Multivalent Catalysts and Multivalent Substrates 170</p> <p>7.7 Conclusions 172</p> <p>Acknowledgements 174</p> <p>References 174</p> <p><b>8 Multivalent Molecular Recognition on the Surface of Bilayer Vesicles 177<br /></b><i>Jens Voskuhl, Ulrike Kauscher, and Bart Jan Ravoo</i></p> <p>8.1 Introduction 177</p> <p>8.2 Molecular Recognition of Vesicles 179</p> <p>8.2.1 Metal Coordination 180</p> <p>8.2.2 Light Responsive Interactions 184</p> <p>8.2.3 Hydrogen Bonding and Electrostatic Interactions 185</p> <p>8.3 Biomimetic Vesicles 188</p> <p>8.3.1 Vesicles as Multivalent Platforms 188</p> <p>8.3.2 Membrane Fusion 193</p> <p>8.4 Vesicle?-based Supramolecular Materials 196</p> <p>8.4.1 Hydrogels 196</p> <p>8.4.2 Immobilization of Vesicles 198</p> <p>8.4.3 Nanoparticles and Nanocontainers 198</p> <p>8.5 Conclusion 201</p> <p>Acknowledgment 201</p> <p>References 201</p> <p><b>Part III Multivalent Systems in Biology 205</b></p> <p><b>9 Blocking Pathogens by Multivalent Inhibitors 207<br /></b><i>Sumati Bhatia, Benjamin Ziem, and Rainer Haag</i></p> <p>9.1 Introduction 207</p> <p>9.2 Design of Multivalent Ligand Architectures 209</p> <p>9.3 Multivalent Carbohydrate Ligands 212</p> <p>9.4 Scaffold Architecture 215</p> <p>9.4.1 Linear and Dendritic Scaffolds 215</p> <p>9.4.2 Multivalent Gold Nanoparticles 218</p> <p>9.4.3 2D Platforms 220</p> <p>9.5 Nano?-and Microgels for Pathogen Inhibition 222</p> <p>9.6 Conclusion 223</p> <p>Acknowledgments 224</p> <p>References 224</p> <p><b>10 Multivalent Protein Recognition Using Synthetic Receptors 229<br /></b><i>Akash Gupta, Moumita Ray, and Vincent M. Rotello</i></p> <p>10.1 Introduction 229</p> <p>10.2 Structural Properties of Protein Surfaces 229</p> <p>10.2.1 Protein–Protein Interfacial Areas 229</p> <p>10.2.2 Chemical Nature of the Protein–Protein Interface 230</p> <p>10.2.3 “Hot Spots” 230</p> <p>10.2.4 O?-Ring Structure 232</p> <p>10.3 Synthetic Receptors for Protein Surface Recognition 232</p> <p>10.3.1 Porphyrin Scaffolds for Protein Surface Recognition 232</p> <p>10.3.2 Protein Surface Recognition Using Molecular Tweezers 238</p> <p>10.3.3 Calixarene Scaffolds for Protein Surface Recognition 240</p> <p>10.3.4 Recognition of Protein Surfaces Using Nanoparticles 243</p> <p>10.3.4.1 Nanoparticles as Protein Mimics 244</p> <p>10.3.4.2 Regulating the Structure and Function of Proteins Using Nanoparticles 246</p> <p>10.3.4.3 Nanoparticle?-based Protein Sensors 250</p> <p>10.4 Future Perspective and Challenges 254</p> <p>Acknowledgment 257</p> <p>References 257</p> <p><b>11 Multivalent Calixarenes for the Targeting of Biomacromolecules 263<br /></b><i>Francesco Sansone and Alessandro Casnati</i></p> <p>11.1 Introduction 263</p> <p>11.2 Binding to Proteins and Enzymes 266</p> <p>11.3 Recognition of Carbohydrate Binding Proteins (Lectins) 273</p> <p>11.4 Binding Polyphosphates, Oligonucleotides and Nucleic Acids 279</p> <p>11.5 Conclusions 284</p> <p>Acknowledgements 285</p> <p>References 285</p> <p><b>12 Cucurbit[n]uril Assemblies for Biomolecular Applications 291<br /></b><i>Emanuela Cavatorta, Luc Brunsveld, Jurriaan Huskens, and Pascal Jonkheijm</i></p> <p>12.1 Introduction 291</p> <p>12.2 Molecular Recognition Properties of CB[n- 293</p> <p>12.2.1 Interactions with the Carbonyl Portals of CB[n- 293</p> <p>12.2.2 Release of High Energy Water Molecules from the CB[n- Cavity 295</p> <p>12.2.3 Enthalpy?-driven Hydrophobic Effect for CB[n- 295</p> <p>12.2.4 Enthalpy?-driven Hydrophobic Effect for CB[8- Heteroternary Complexes 297</p> <p>12.3 Control Over the Binding Affinity with CB[n- 299</p> <p>12.4 CB[n] Recognition of Amino Acids, Peptides, and Proteins 301</p> <p>12.5 CB[n] for Bioanalytical and Biomedical Applications 305</p> <p>12.5.1 CB[n]-mediated Assembly of Bioactive Polymers and Hydrogels 305</p> <p>12.5.2 CB[n]-mediated Assembly of Bioactive Nanoparticles 307</p> <p>12.5.3 CB[n]?-mediated Assembly on Bioactive Surfaces 313</p> <p>12.6 Conclusions and Outlook 317</p> <p>Acknowledgment 319</p> <p>References 319</p> <p><b>13 Multivalent Lectin–Glycan Interactions in the Immune System 325<br /></b><i>Joao T. Monteiro and Bernd Lepenies</i></p> <p>13.1 Introduction 325</p> <p>13.2 Targeting Innate Immunity to Shape Adaptive Immunity 327</p> <p>13.3 C?-type Lectin Receptors 328</p> <p>13.3.1 Multivalent Glycoconjugates Targeting DC?-SIGN 331</p> <p>13.3.2 Multivalent Glycoconjugates Targeting Other CLRs 331</p> <p>13.4 Galectins 332</p> <p>13.5 Siglecs 334</p> <p>13.6 Conclusions 335</p> <p>Acknowledgment 335</p> <p>References 335<br /><br /></p> <p><b>14 Blocking Disease Linked Lectins with Multivalent Carbohydrates 345<br /></b><i>Marjon Stel and Roland J. Pieters</i></p> <p>14.1 Introduction 345</p> <p>14.2 Haemagglutinin 347</p> <p>14.3 LecA 349</p> <p>14.4 LecB 354</p> <p>14.5 Galectins 358</p> <p>14.6 Concanavalin A 362</p> <p>14.7 Cholera Toxin 366</p> <p>14.8 Propeller Lectins 367</p> <p>14.9 Conclusion 371</p> <p>Acknowledgements 371</p> <p>References 371</p> <p>Index 381</p>