Multivalency

List of Contributors xi Foreword xv Preface xvii Part I General Introduction to Multivalent Interactions 1 1 Additivity of Energy Contributions in Multivalent Complexes 3 Hans?-Jorg Schneider 1.1 Introduction 3 1.2 Additivity of Single Interactions - Examples 3 1.3 Limitations of Additivity 7 1.3.1 Free Energy Values DeltaG Instead of Enthalpic and Entropic Values DeltaH, TDeltaS 7 1.3.2 Mismatch as Limitation of Additivity 9 1.3.3 Medium Effects as Limiting Factor 12 1.3.4 Strain and Induced Fit 12 1.4 Cooperativity 13 1.5 Allostery 14 1.6 Conclusions 17 References 18 2 Models and Methods in Multivalent Systems 23 Jurriaan Huskens 2.1 Introduction 23 2.1.1 General Introduction 23 2.1.2 Multivalent versus Cooperative Interactions 24 2.2 Numerical Data Analysis 25 2.2.1 Model Simulations Using a Spreadsheet Approach 26 2.2.2 Setting Up and Assessing Titrations 30 2.2.3 Using Spreadsheet Simulations to Fit Experimental Data to a Model 36 2.3 Models for Multivalent Systems 41 2.3.1 The Simplest Multivalent System: A 1:1 Complex with Two Interaction Sites 41 2.3.2 Multivalent Binding at Surfaces 46 2.4 Special Multivalent Systems 53 2.4.1 Increasing the Valency of Interfacial Assemblies: Dendrimers, Oligomers, and Polymers 53 2.4.2 Heterotropic Interactions 58 2.4.3 Kinetics and Dynamics 63 2.5 Conclusions 68 Acknowledgments 68 References 68 3 Design Principles for Super Selectivity using Multivalent Interactions 75 Tine Curk, Jure Dobnikar, and Daan Frenkel 3.1 Introduction 75 3.1.1 Background: Ultra?-sensitive Response 75 3.2 Super selectivity: An emergent property of multivalency 78 3.3 Multivalent Polymer Adsorption 84 3.4 Which Systems are Super Selective? 86 3.4.1 Rigid Geometry Interactions 86 3.4.2 Disordered Multivalency 87 3.5 Design Principles for Super?-Selective Targeting 90 3.6 Summary: It is interesting, but is it useful? 93 Appendix 3.A: What Is Effective Molarity? 95 Acknowledgements 98 References 98 4 Multivalency in Biosystems 103 Jens Dernedde 4.1 Introduction 103 4.2 Cell-Cell Adhesion 104 4.2.1 Homotypic Interactions, Cadherins Keep Cells Together 105 4.2.2 Selectins, Heterotypic Cell Adhesion to Fight Infections 106 4.2.3 Bacterial Adhesion by FimH 108 4.3 Phase Transition, Multivalent Intracellular Assemblies 109 4.4 Multivalency in the Fluid Phase, Pathogen Opsonization 111 4.5 Conclusion 113 Acknowledgment 113 References 114 Part II Multivalent Systems in Chemistry 121 5 Multivalency in Cyclodextrin/Polymer Systems 123 Akihito Hashidzume and Akira Harada 5.1 Introduction 123 5.2 General Perspectives of Multivalency in Cyclodextrin/Polymer Systems 125 5.3 Typical Examples of Multivalency in Cyclodextrin/Polymer Systems 126 5.3.1 Formation of Polymer Aggregates from Cyclodextrin?-Polymers and Guest?-Polymers 126 5.3.2 Selectivity of Interaction Enhanced by Multivalency 127 5.3.3 Self?-Healable Hydrogels Based on Multivalency 134 5.4 Summary and Outlook 136 Acknowledgments 136 References 138 6 Cucurbit[n-uril?-Mediated Multiple Interactions 143 Zehuan Huang and Xi Zhang 6.1 Introduction to Cucurbit[n-uril Chemistry 143 6.2 Heteroternary Complexes 143 6.3 Homoternary Complexes 146 6.4 Conclusions 150 References 150 7 Multivalency as a Design Criterion in Catalyst Development 153 Paolo Scrimin, Maria A. Cardona, Carlos M. Leon Prieto, and Leonard J. Prins 7.1 Introduction 153 7.2 Formation of Enzyme?-Like Catalytic Pockets 154 7.3 Cooperativity Between Functional Groups 157 7.4 Mechanistic Effects 161 7.5 The Dendritic Effect in Multivalent Nanozymes 164 7.5.1 Peptide?-Based Dendrimers for the Cleavage of Phosphodiesters 166 7.5.2 Catalytic 3D SAMs on Au NPs 168 7.6 Multivalent Catalysts and Multivalent Substrates 170 7.7 Conclusions 172 Acknowledgements 174 References 174 8 Multivalent Molecular Recognition on the Surface of Bilayer Vesicles 177 Jens Voskuhl, Ulrike Kauscher, and Bart Jan Ravoo 8.1 Introduction 177 8.2 Molecular Recognition of Vesicles 179 8.2.1 Metal Coordination 180 8.2.2 Light Responsive Interactions 184 8.2.3 Hydrogen Bonding and Electrostatic Interactions 185 8.3 Biomimetic Vesicles 188 8.3.1 Vesicles as Multivalent Platforms 188 8.3.2 Membrane Fusion 193 8.4 Vesicle?-based Supramolecular Materials 196 8.4.1 Hydrogels 196 8.4.2 Immobilization of Vesicles 198 8.4.3 Nanoparticles and Nanocontainers 198 8.5 Conclusion 201 Acknowledgment 201 References 201 Part III Multivalent Systems in Biology 205 9 Blocking Pathogens by Multivalent Inhibitors 207 Sumati Bhatia, Benjamin Ziem, and Rainer Haag 9.1 Introduction 207 9.2 Design of Multivalent Ligand Architectures 209 9.3 Multivalent Carbohydrate Ligands 212 9.4 Scaffold Architecture 215 9.4.1 "Soft" Linear and Dendritic 215 9.4.2 Rigid Core Multivalent Nanoparticles 218 9.5 2 D Platforms 220 9.6 Nano?-and Microgels for Pathogen Inhibition 222 9.7 Conclusion 223 Acknowledgments 224 References 224 10 Multivalent Protein Recognition Using Synthetic Receptors 229 Akash Gupta, Moumita Ray, and Vincent M. Rotello 10.1 Introduction 229 10.2 Structural Properties of Protein Surfaces 229 10.2.1 Protein-Protein Interfacial Areas 229 10.2.2 Chemical Nature of the Protein-Protein Interface 230 10.2.3 "Hot Spots" 230 10.2.4 O?-Ring Structure 232 10.3 Synthetic Receptors for Protein Surface Recognition 232 10.3.1 Porphyrin Scaffolds for Protein Surface Recognition 232 10.3.2 Protein Surface Recognition Using Molecular Tweezers 238 10.3.3 Calixarene Scaffolds for Protein Surface Recognition 240 10.3.4 Recognition of Protein Surfaces Using Nanoparticles 243 10.3.4.1 Nanoparticles as Protein Mimics 244 10.3.4.2 Regulating the Structure and Function of Proteins Using Nanoparticles 246 10.3.4.3 Nanoparticle?-based Protein Sensors 250 10.4 Future Perspective and Challenges 254 Acknowledgment 257 References 257 11 Multivalent Calixarenes for the Targeting of Biomacromolecules 263 Francesco Sansone and Alessandro Casnati 11.1 Introduction 263 11.2 Binding to Proteins and Enzymes 266 11.3 Recognition of Carbohydrate Binding Proteins (Lectins) 273 11.4 Binding Polyphosphates, Oligonucleotides and Nucleic Acids 279 11.5 Conclusions 284 Acknowledgements 285 References 285 12 Cucurbit[n-uril Assemblies for Biomolecular Applications 291 Emanuela Cavatorta, Luc Brunsveld, Jurriaan Huskens, and Pascal Jonkheijm 12.1 Introduction 291 12.2 Molecular Recognition Properties of CB[n- 293 12.2.1 Interactions with the Carbonyl Portals of CB[n- 293 12.2.2 Release of High Energy Water Molecules from the CB[n- Cavity 295 12.2.3 Enthalpy?-driven Hydrophobic Effect for CB[n- 295 12.2.4 Enthalpy?-driven Hydrophobic Effect for CB[8- Heteroternary Complexes 297 12.3 Control Over the Binding Affinity with CB[n- 299 12.4 CB[n- Recognition of Amino Acids, Peptides, and Proteins 301 12.5 CB[n- for Bioanalytical and Biomedical Applications 305 12.5.1 CB[n-?-mediated Assembly of Bioactive Polymers and Hydrogels 305 12.5.2 CB[n-?-mediated Assembly of Bioactive Nanoparticles 307 12.5.3 CB[n-?-mediated Assembly on Bioactive Surfaces 313 12.6 Conclusions and Outlook 317 Acknowledgment 319 References 319 13 Multivalent Lectin-Glycan Interactions in the Immune System 325 Joao T. Monteiro and Bernd Lepenies 13.1 Introduction 325 13.2 Targeting Innate Immunity to Shape Adaptive Immunity 327 13.3 C?-type Lectin Receptors 328 13.3.1 Multivalent Glycoconjugates Targeting DC?-SIGN 331 13.3.2 Multivalent Glycoconjugates Targeting Other CLRs 331 13.4 Galectins 332 13.5 Siglecs 334 13.6 Conclusions 335 Acknowledgment 335 References 335 14 Blocking Disease Linked Lectins with Multivalent Carbohydrates 345 Marjon Stel and Roland J. Pieters 14.1 Introduction 345 14.2 Haemagglutinin 347 14.3 LecA 349 14.4 LecB 354 14.5 Galectins 358 14.6 Concanavalin A 362 14.7 Cholera Toxin 366 14.8 Propeller Lectins 367 14.9 Conclusion 371 Acknowledgements 371 References 371 Index