Preface xi Abbreviations xiii PART I Chemistry Toolbox 1 1. Overview of Peptidomimetic Concepts and Design 3 1.1 Introduction 3 1.2 Definition and Classification 5 1.3 In Silico Tools for Peptidomimetic Design 7 1.4 Overview of Synthetic Approaches Toward Peptidomimetics 11 1.5 Amino Acid and Peptide Bioisosterism 14 1.6 Local Modifications: The Tethering Approach 18 1.
7 Heterocyclic Peptidomimetics 19 1.8 Global Restrictions 23 1.9 Therapeutic and Diagnostic Applications of Peptidomimetics 29 1.10 Conclusion 33 2. Multicomponent Reactions Toward Peptidomimetics 41 2.1 Introduction 41 2.2 Isocyanide-Based MCRs 43 2.3 Imine-Based MCRs 49 2.
4 Tandem MCRs 54 2.5 Combination of MCRs with Other Processes 55 2.6 Biological Applications of MCRs in Peptidomimetic Design 56 2.7 Conclusion 59 3. Non-Coded Amino Acids: Cyclic Scaffolds and C--H Functionalization 65 3.1 Introduction 65 3.2 Cyclic Amino Acids 65 3.3 Principles of C--H Functionalization 77 3.
4 C--H Functionalization of Amino Acids 83 3.5 Conclusion 90 4. Late-Stage Functionalization of Peptides 97 4.1 Introduction 97 4.2 Classification of Late-Stage Functionalization of Peptides 100 4.3 Backbone Modification 103 4.4 Side-Chain Functionalization 109 4.5 Conclusion 117 PART II Peptidomimetic Compounds 123 5.
Macrocyclic Peptides and Peptidomimetics 125 5.1 Introduction 125 5.2 Classification of Macrocyclic Peptides 127 5.3 Peptide Macrocyclization Chemistry 127 5.4 Case Studies of Macrocyclic Peptides in Drug Discovery Applications 147 5.5 Conclusion 153 6. Stapled Peptides 159 6.1 Introduction 159 6.
2 Strategic Approaches for Peptide-Stapling Design 161 6.3 Chemical Methods for Peptide Stapling 164 6.4 Therapeutic Applications 175 6.5 Conclusion 179 7. Advances in Peptidomimetic Foldamers 187 7.1 Introduction 187 7.2 Secondary-Structure Mimetics 189 7.3 Peptidomimetic Foldamers 190 7.
4 Application of Secondary-Structure Mimetic Foldamers in Drug Discovery 198 7.5 Conclusion 202 PART III Applications and Case Studies in Drug Discovery 209 8. Peptidomimetic SARS-CoV-2 Main Protease Inhibitors 211 8.1 Introduction 211 8.2 Structure and Replication Cycle of SARS-CoV-2 212 8.3 Approved Vaccines and Antiviral Treatments 214 8.4 Therapeutic Targets and Approaches 215 8.5 Structure and Function of the Main Protease (Mpro) 216 8.
6 Peptidomimetic Mpro Inhibitors 219 8.7 The Road to Approval of Paxlovid as an Mpro Inhibitor Drug 224 8.8 PROTACs in Antiviral Drug Discovery Through Target Degradation 227 8.9 Conclusion 228 9. Antimicrobial Peptidomimetics 237 9.1 Introduction 237 9.2 Bacterial Resistance Mechanisms 238 9.3 Definition of Antimicrobial Peptides 240 9.
4 Classification of Antimicrobial Peptides 240 9.5 Structural and Physicochemical Determinants of Antimicrobial Peptides 242 9.6 Mechanism of Action of Antimicrobial Peptides 244 9.7 Representative Examples of Antimicrobial Peptides 246 9.8 Antimicrobial Peptidomimetics 248 9.9 Conclusion 253 10. Principles and Case Studies of Peptidomimetic Inhibitors of PPI 259 10.1 Introduction 259 10.
2 Design of Peptidomimetic PPI Inhibitors 261 10.3 Peptidomimetics Targeting Cancer PPI 261 10.4 Case Study in Cancer: Targeting the p53-MDM2 PPI 262 10.5 Case Study in Infectious Diseases: Targeting the ACE2-SARS-CoV-2 Spike Protein PPI 270 10.6 Conclusion 278 11. Peptidomimetics Targeting the Alzheimer''s Disease 285 11.1 Introduction 285 11.2 The Amyloid Hypothesis 289 11.
3 Therapeutic Strategies for Alzheimer''s Disease 291 11.4 BACE1 Inhibitors 299 11.5 BACE1 Inhibitors in Clinical Trials 303 11.6 Toward Selective BACE1 Inhibitors 304 11.7 Conclusion 305 12. Peptidomimetic Drugs 313 12.1 Introduction 313 12.2 Nirmatrelvir 314 12.
3 Voxilaprevir 317 12.4 Brilacidin 320 12.5 Murepavadin 322 12.6 Ixazomib 324 12.7 Venetoclax 326 12.8 Lu-PSMA-617 328 12.9 Trofinetide 330 12.10 Tavilermide 332 12.
11 Difelikefalin 333 12.12 Macimorelin 334 References 335 Index 341.