De Novo Peptide Design: Principles and Applications

Front Cover
De Novo Peptide Design
Copyright Page
Dedication
Contents
List of contributors
1 Structural organization of peptides
1.1 Molecular interactions for protein folding
1.1.1 Hydrogen bonds
1.1.2 CH−π interactions
1.1.3 van der Waals interactions
1.1.4 Hydrophobic interaction
1.1.5 Electrostatic interactions
1.1.6 Aromatic−aromatic (π−π) interactions
1.1.7 Cation−π interaction
1.2 Poly-alanine models and the energetics of protein folding
1.3 De novo protein design and stereochemical logic of protein folding
1.3.1 Stereochemical principles in protein design
1.3.2 β-Turn as stereochemically diverse conformational nucleators
1.3.2.1 Homochiral turns
1.3.2.2 Heterochiral turns
1.3.3 Design of β-sheet proteins
1.3.3.1 β-hairpin design
1.3.3.2 Multiple stranded sheets
1.3.3.3 Mixed αβ-protein design
1.3.4 All α-helix protein design
1.3.5 Metalloprotein design
1.4 Shape-specific design of heterochiral proteins
1.5 Enzymes: functional proteins
1.5.1 Hydrolase enzymes
References
2 Modeling and simulation of peptides
2.1 Introduction
2.2 Peptide design
2.2.1 Ligand-based peptide design
2.2.1.1 Sequence-based methods
2.2.1.2 Property-based methods
2.2.1.3 Conformation-based methods
2.2.2 Target-based peptide design
2.2.3 De novo peptide design
2.3 Prediction of peptide structure
2.4 In silico validation of design by molecular dynamic simulations
2.4.1 Temperature and pressure coupling
2.4.2 Energy minimization
2.4.2.1 Steepest descent method
2.4.2.2 Conjugate gradient method
2.4.2.3 Newton−Raphson methods
2.4.3 Force field
2.4.3.1 Lennard-Jones potential
2.4.3.2 Coulomb potential
2.4.4 Conformational analysis
2.4.5 Case studies of molecular dynamics simulations and trajectory analysis
2.4.5.1 Antimicrobial activity
2.4.5.2 Drug delivery
2.5 Conclusion
References
3 Solid phase peptide synthesis
3.1 Introduction
3.2 Principles of solid phase peptide synthesis
3.2.1 Merrifield solid phase peptide synthesis or Boc/Bzl
3.2.2 Fmoc/tBu solid phase peptide synthesis
3.3 Resins
3.4 Linkers
3.5 Side-chain protecting groups
3.6 Coupling reaction
3.7 Fmoc deprotection
3.8 Final cleavage
3.9 Side reactions
3.9.1 Diketopiperazine formation
3.9.2 Aspartimide formation
References
4 Peptide-based Antibiotics
4.1 Introduction
4.2 Antimicrobial peptides
4.3 De novo design of antimicrobial peptides
4.3.1 Unnatural amino acids
4.3.2 Cyclization
4.3.3 Chemical modifications
4.3.3.1 Lipidation
4.3.3.2 Acylation
4.3.3.3 Glycosylation
4.3.4 Conjugation to conventional antibiotics
4.3.5 Multivalent approach
4.3.6 Antimicrobial peptide mimics
4.4 Antimicrobial peptides: Strategy to combat antimicrobial resistance
4.5 Mechanism of action and selectivity of antimicrobial peptides
4.5.1 Barrel-stave model
4.5.2 Carpet model
4.5.3 Toroidal model
4.5.4 Disordered toroidal-pore model
4.6 Strengths and weakness of antimicrobial peptides
4.6.1 Merits of antimicrobial peptides
4.6.2 Limitations of antimicrobial peptides
4.7 Conclusion
References
5 Cell-penetrating peptides
5.1 Cell-penetrating peptides: a brief history
5.2 Classification of cell-penetrating peptides
5.2.1 Cationic cell-penetrating peptides
5.2.2 Amphipathic cell-penetrating peptides
5.2.2.1 Primary amphipathic
5.2.2.2 Secondary amphipathic α-helical cell-penetrating peptides
5.3 Mechanism of uptake
5.3.1 Interaction with cell surface
5.3.1.1 Role of proteoglycans
5.3.1.2 Role of cellular receptors
5.3.1.3 Interaction with membrane phospholipids
5.3.2 Cellular internalization of cell-penetrating peptides
5.3.2.1 Endocytosis
5.3.2.2 Direct penetration
5.3.3 Cellular localization
5.3.4 Transcellular transport and degradation
5.4 Strengths, limitations, and opportunities
5.5 Cell-type specificity: to be or not to be
5.6 Cell-penetrating peptides for anticancer drug delivery
5.6.1 Cell-penetrating peptides for targeted delivery
5.6.2 Delivery of anticancer drugs using cell-penetrating peptides
5.7 Cell-penetrating peptide prediction
5.8 Designing cell-penetrating peptides
5.8.1 Amino acid sequence
5.8.1.1 Chirality
5.8.1.2 Cationic charge
5.8.1.3 Hydrophobicity and aromaticity
5.8.2 Secondary structure folding and its effects on cellular uptake
5.9 Conclusion
References
6 Peptide-based nanomaterials: applications and challenges
6.1 Introduction to molecular self-assembly
6.2 Protein and peptide self-assembly
6.3 Peptide-based nanomaterials
6.3.1 Amyloid peptides
6.3.2 Cyclic peptides
6.3.3 Peptide amphiphiles
6.3.3.1 Lipopeptides
6.3.3.2 Peptide-only amphiphiles
6.3.3.3 Bolaamphiphiles
6.3.4 Turn containing peptides
6.3.5 Aromatic-moiety containing peptides and amino acids
6.4 Applications of peptide-based nanomaterials
6.5 Conclusion, challenges, and future directions
References
7 Peptide nanocatalysts
7.1 Introduction
7.2 Types of catalysts
7.2.1 Homogeneous catalysts
7.2.2 Heterogeneous catalysts
7.2.3 Nanocatalysts
7.2.3.1 Effect of size
7.2.3.2 Effect of shape
7.2.3.3 Effect of composition
7.3 Enantioselectivity in catalytic reactions
7.4 Enzyme catalysis
7.4.1 Enzyme active site
7.4.1.1 Proximity and orientation effect
7.4.1.2 Proton donors or acceptors
7.5 Enzyme mimetics
7.5.1 Single amino acid mutations can impart high catalytic activity onto a protein
7.5.2 Incorporation of unnatural amino acids as a minimalistic approach for enzyme design
7.5.3 De novo design of peptide-based enzyme mimics
7.5.4 Peptide-based minimalist approach of enzyme catalysis
7.6 Structural design of the artificial peptide-based enzyme
7.6.1 Optimization of the catalytic microenvironment
7.7 Self-assembling peptide catalysts
7.8 Peptide mimics with enhanced catalytic efficiency
7.9 Peptide-based artificial metalloenzyme
7.10 Exploring unnatural amino acids for de novo peptide-based metalloenzymes
7.11 Aldolase mimic
7.11.1 Metal ion-free aldolase mimic (Type I aldolases)
7.12 Hydrolase mimic
7.13 Oxidase mimic
7.13.1 Lytic polysaccharide monooxygenase
7.14 Conclusions and future prospects
References
8 Bioinspired functional molecular constructs
8.1 Introduction
8.2 Peptide-based functional materials
8.2.1 De novo designed fluorescent peptide
8.2.2 De novo designed antimicrobial peptides
8.2.3 De novo designed cell-penetrating and tumor homing peptide
8.2.4 De novo designed biocatalysts
8.2.4.1 Proline-based supramolecular catalyst
8.2.4.2 Histidine-based supramolecular catalyst
8.2.4.3 Peptide catalyst with metal ions
8.2.5 Peptide-based smart materials
8.2.5.1 Stimulus-responsive materials
8.2.5.2 Peptide-based molecular shuttles
8.2.5.3 Peptide-based metal organic frameworks
8.2.5.4 Peptide-based vaccines
8.3 De novo designed peptide nano-assemblies
8.3.1 Nanotubes
8.3.2 Nanosheets
8.3.3 Cyclic peptides
8.3.4 Nanofibers
8.3.5 Hydrogels
8.3.5.1 Single amino acid-based hydrogels
8.3.5.2 Short and ultrashort peptide-based hydrogel
8.3.5.3 Stimulus-responsive peptide hydrogel
8.3.5.4 Amyloid-based hydrogels
8.3.5.5 Fmoc-based hydrogels
8.4 Properties of self-assembled nanostructures
8.4.1 Mechanical properties
8.4.2 Electrical properties
8.4.3 Optical properties
8.5 Factors affecting nanoassemblies
8.5.1 Aromatic π−π interactions
8.5.2 Hydrogen bonding
8.5.3 Hydrophobic interactions
8.5.4 Electrostatic interactions
8.5.5 Van der Waals interactions
8.5.6 Solvent effects
8.6 Applications of de novo designed peptide constructs
8.6.1 Tissue engineering
8.6.2 Drug delivery systems
8.6.3 Antimicrobial peptide hydrogel for wound healing
8.6.4 Biosensors
8.7 Conclusion and future directions
References
9 Patents in peptide science
9.1 Introduction
9.2 Basics of protein and peptide structure
9.2.1 Patents
9.3 Modeling and simulation of peptides
9.3.1 Patents
9.4 Glucagon-like peptide-1 analogs
9.4.1 Patents
9.5 Peptide-based antibiotics
9.5.1 Patents
9.6 Drug delivery vehicles
9.6.1 Patents
9.7 Protein aggregation
9.7.1 Patents
9.8 Peptide nanomaterials
9.8.1 Patents
9.9 Peptide-based hydrogels
9.9.1 Patents
9.10 Therapeutic interventions against protein/peptide aggregation diseases
9.10.1 Patents
9.11 Computational tools and algorithms in peptide design
9.11.1 Patents
References
Index
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