Antimicrobial Peptides

A Roadmap for Accelerating Discovery and Development

1st Edition - November 22, 2024
Imprint: Elsevier
Editors: Luis H. Reyes, Juan C. Cruz, Gregory R. Wiedman
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 1 5 3 9 3 - 8
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 5 3 9 4 - 5

Antimicrobial Peptides: A Roadmap for Accelerating Discovery and Development covers the most important efforts of scientists and engineers worldwide to accelerate the process o… Read more

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Antimicrobial Peptides: A Roadmap for Accelerating Discovery and Development covers the most important efforts of scientists and engineers worldwide to accelerate the process of discovery, production, and eventual market penetration of more potent antimicrobial peptides. These efforts have been fueled by emerging technologies such as artificial intelligence and data science, molecular and CFD simulations, easy-to-use process simulation packages, microfluidics, 3D-printing, among many others. Such technologies can now be implemented and scaled up quickly and at relatively low cost in low-budget production facilities, critical to moving to sustainable and marketable products worldwide.

Discovering novel antimicrobial peptides rationally and cost-effectively has emerged as one of the significant challenges of modern biotechnology. Thus far, this process has been tedious and costly, resulting in molecules with activities far below those needed to address the current challenge of microbial resistance to antibiotics that takes the lives of thousands of people around the world every year. Finally, the book also highlights how multidisciplinary teams have assembled to address the challenges of manufacturing, biological testing, and clinical trials to finally reach complete translation.

Antimicrobial Peptides
Cover image
Title page
Table of Contents
Copyright
Contributors
Introduction—Antimicrobial peptides: From the bench to the bedside
References
Section A: Computational approaches
Chapter 1 Bioinformatic methods for the design of antimicrobial peptides
Abstract
Keywords
1 Introduction
1.1 The significance of bioinformatics in accelerating the discovery and optimization of AMPs
2 Foundations of AMP design
2.1 Bioinformatics-driven peptide engineering
2.2 Computational tools for AMP discovery
2.3 Bioinformatic resources for AMP discovery
2.4 Theoretical frameworks for AMP structure-activity relationship (SAR)
3 Stability and toxicity prediction
3.1 Stability of AMPs in biological contexts
3.2 Toxicity toward mammalian cells
3.3 Predictive models for stability and toxicity
3.4 Computational methods for predicting peptide stability
3.5 Toxicity prediction models
4 Formulation and delivery system design
4.1 Challenges in AMP formulation: Addressing stability, bioavailability, and controlled release in therapeutic applications
4.2 Integration of computational approaches
4.3 Bioinformatics in formulation design
4.4 QSAR models in formulation optimization
4.5 Innovations in AMP delivery: Bioinformatic tools and design of advanced delivery systems
5 Conclusion
5.1 Summary of key points: The vital role of bioinformatics in the discovery and development of next-generation AMPs
5.2 Future directions: Emerging trends and technologies in bioinformatics that could revolutionize the design and application of AMPs
5.3 Final thoughts on the integration of bioinformatics into multidisciplinary strategies for combating antibiotic resistance
References
Chapter 2 Fundamentals of molecular dynamics for antimicrobial peptides’ discovery
Abstract
Keywords
1 Introduction
2 MD fundamentals
2.1 Force fields for AMPs
3 Applications of MD in AMP discovery
4 Recent advances in MD simulations for AMP discovery
4.1 Hybrid QM/MM simulations for AMPs
4.2 Machine learning methods for MD simulations
5 Summary
References
Chapter 3 Artificial intelligence for the discovery of antimicrobial peptides
Abstract
Keywords
1 Introduction
2 Data
3 Traditional machine learning
3.1 Features
3.2 Methods
3.3 Examples
4 Deep learning
4.1 Architectures
4.2 Data representation and use cases
5 Metrics
6 Postprocessing of candidates
7 AI for peptide-related tasks
8 AI for similar tasks in the biological field
References
Chapter 4 Computational tools for handling large databases of biological relevance
Abstract
Keywords
1 Introduction
2 AMP databases
2.1 General AMPs databases
2.2 Specific AMPs databases
3 Web scraping for biological databases
4 Programming languages and their tools
4.1 Python
4.2 R libraries and packages
5 Practical implementation examples
6 Recommendations for best practices
6.1 Validate databases
6.2 Data gathering
6.3 Efficient data curation
6.4 Implement filters
6.5 Dataset balancing
6.6 Homology and redundancy reduction
6.7 Feature extraction
7 Conclusions
References
Chapter 5 Statistical analysis and data interpretation
Abstract
Keywords
1 Introduction
2 Descriptive statistics
2.1 Measures of central tendency
2.2 Measures of dispersion
2.3 Importance in data interpretation and preprocessing
3 Inferential statistics
3.1 Hypothesis testing
3.2 Confidence intervals
3.3 t-Tests
3.4 Analysis of variance (ANOVA)
3.5 Chi-square tests
3.6 Correlation and regression analyses
4 Multivariate statistical analysis
4.1 Principal component analysis (PCA)
4.2 Factor analysis
4.3 Cluster analysis
4.4 Discriminant analysis
4.5 Applications in antimicrobial peptide research
5 Data processing tools
5.1 Data preprocessing
5.2 Data imputation
5.3 Data visualization
5.4 Software and programming languages for data analysis
6 Interpreting computational data
6.1 Avoiding common pitfalls
6.2 Importance of reproducibility
6.3 Evaluating the significance and impact of findings
7 Conclusion
References
Section B: Experimental approaches
Chapter 6 Chemical synthesis of peptides: Conventional and novel routes
Abstract
Keywords
1 Selection of the solid support
2 Protection and deprotection strategy of α-groups
3 Side group protection
4 Activation and coupling strategy
5 Cleavage strategy in solid-phase peptide synthesis
6 Peptide lipidation strategy
7 Cyclization strategy
8 Purification strategy
8.1 Troubleshooting
9 Emerging methods in antimicrobial peptide synthesis
References
Chapter 7 Biological platforms for the production of antimicrobial peptides: Bacterial, yeast, and cell-free systems
Abstract
Keywords
1 Bacterial hosts for antimicrobial peptide production
1.1 Masking the AMP: Using protein fusion strategies
1.2 Direct expression
2 Exploring the use of fungi for antimicrobial peptide production
2.1 Expression systems
3 Cell-free synthesis: Revolutionizing biotherapeutic manufacturing
3.1 Biosafety
3.2 High-throughput and on-demand production
4 Exploring the drivers and challenges of biological antimicrobial production
4.1 Motives for utilizing a biological approach for the production of AMPs
4.2 Challenges
5 Future perspectives
5.1 Novel expression systems for AMPs
5.2 In vivo activity and safety
6 Conclusion
7 AI disclosure
References
Chapter 8 Biological platforms for the production of antimicrobial peptides: Plants, insects, and mammalian cells systems
Abstract
Keywords
1 Expression of antimicrobial peptides in plants
1.1 Heterologous expression
1.2 Direct gene transfer
1.3 Plant expression systems
1.4 Factors impacting plant expression systems
2 Insect cell-based expression systems for antimicrobial peptide production
3 Technologies for expressing antimicrobial peptides in mammalian cells
3.1 Recombinant DNA technology
3.2 Synthetic biology
3.3 mRNA-based expression systems
4 Exploring the drivers and challenges of biological antimicrobial production in plants, insects, and mammalian cell systems
4.1 Motives for utilizing plant, insect, and mammalian cell systems for the production of AMPs
4.2 Challenges
5 Future perspectives
5.1 Novel expression systems for AMPs
5.2 In vivo activity and safety
6 Conclusion
7 AI disclosure
References
Chapter 9 Classical and emerging approximations for the screening of antimicrobial peptide libraries
Abstract
Keywords
1 Introduction
1.1 Importance of screening peptide libraries
1.2 Overview of classical and emerging approximations for screening peptide libraries
2 Classical screening technologies for peptide libraries
2.1 Phage display
2.2 Ribosome display
2.3 Cell-surface display
2.4 Advantages and disadvantages of classical screening technologies
3 Emerging technologies for peptide library screening
3.1 Microfluidics-based screening
3.2 Other emerging technologies
3.3 Advantages and disadvantages of emerging screening technologies
4 Approaches to monitoring screening in real time
4.1 Label-free detection methods
4.2 Fluorescence-based detection methods
4.3 Mass spectrometry-based detection methods
4.4 Surface plasmon resonance (SPR)-based detection methods
5 Proven schemes for screening peptide libraries
5.1 High-throughput screening (HTS)
5.2 Fluorescence-activated cell sorting (FACS)
5.3 Magnetic-activated cell sorting (MACS)
5.4 Microarray screening
6 Technical challenges in screening peptide libraries
6.1 Sensitivity and specificity
6.2 Integration of technologies
7 Future perspectives
8 AI disclosure
References
Chapter 10 Scaling-up of biological production processes
Abstract
Keywords
1 Introduction to scale-up of AMPs production
2 Culture strategies for AMPs production in bioreactor
3 Strategies to scale up a bioreactor for the AMPs production
4 Tools to scale-up the AMP’s production
4.1 Kinetic models for cell growth and mathematical modeling
4.2 Computational fluid dynamics tool for AMPs production
4.3 Scaling-up simulation with SuperPro Designer
References
Chapter 11 Downstream processing for antimicrobial peptide production
Abstract
Keywords
1 Introduction
2 Cell disruption
2.1 High-pressure homogenization
2.2 Sonication
2.3 Enzymatic lysis
2.4 Mechanical milling
3 Harvesting and recovery of antimicrobial peptides
3.1 Centrifugation
3.2 Filtration or tangential filtration
3.3 Sedimentation
3.4 Influencing factors on recovery efficiency
4 Concentration and purification of antimicrobial peptides
4.1 Precipitation methods
4.2 Dialysis and desalting techniques
4.3 Chromatography methods for purification
4.4 Peptide purification by ion exchange chromatography
4.5 Peptide purification by reversed-phase chromatography and hydrophobic interaction chromatography
5 Conclusions
References
Chapter 12 Physicochemical and biochemical characterization of antimicrobial peptides
Abstract
Keywords
1 Introduction
2 Physicochemical characterization
2.1 Molecular weight determination
2.2 Amino acid composition
2.3 Peptide sequence analysis
2.4 Secondary structure analysis
2.5 Tertiary structure analysis
2.6 Hydrophobicity and hydrophilicity
2.7 Charge and pH dependence
2.8 Solubility
2.9 Thermal stability
2.10 Aggregation and oligomerization
3 Biochemical characterization of AMPs
3.1 Pharmacokinetics
3.2 Bioavailability and stability
3.3 Peptide-lipid interactions
3.4 Receptor affinity techniques
3.5 Antiinflammatory and immunomodulatory properties
4 Conclusions
AI Disclosure
References
Section C: Translational studies
Chapter 13 Biological characterization of antimicrobial peptides: In vitro and in vivo studies
Abstract
Keywords
1 Introduction
2 In vitro studies
2.1 Cellular toxicity
2.2 Antimicrobial activity determination
2.3 Mechanism of action
3 In vivo studies
3.1 Systemic viral infection
3.2 Skin infection and wound healing models
3.3 Respiratory tract infection
3.4 Foreign body infection
3.5 Intraperitoneal infections
3.6 Urinary tract infection
3.7 Eye infection
3.8 Thigh muscle infection models
3.9 Bone infection models
3.10 Ex vivo pig skin model
4 Conclusion
References
Chapter 14 Preclinical and clinical studies
Abstract
Keywords
1 Introduction
2 FDA-approved AMP
2.1 Gramicidin
2.2 Polymyxin (E and B)
2.3 Bacitracin
2.4 Vancomycin
2.5 Dalbavancin
2.6 Telavancin
2.7 Oritavancin
2.8 Daptomycin
2.9 Final remarks
3 AMPs that have reached clinical trials
3.1 AMPs for the treatment of skin and soft tissues
3.2 AMPs for the treatment of epithelial infections
3.3 AMPs for the treatment of meningitis and the nervous system
4 Conclusions
References
Chapter 15 Formulation and product design
Abstract
Keywords
1 Systematic approaches for product design
1.1 The integrated product and process design (IPPD)
1.2 Quality by design (QbD)
2 Oral dosage forms
2.1 Tablets
2.2 Capsules
2.3 Characterization
3 Colloidal systems
3.1 Emulsions
4 AMP-based products
4.1 Formulation of AMP-based products
5 Challenges
References
Chapter 16 Packaging, long-term stability, and usability of antimicrobial peptide products
Abstract
Keywords
1 Introduction to packaging in consumer goods
2 Preservation of AMPs: Matrices and conditions
2.1 Preservation in freeze-dried state and aqueous solutions
2.2 Preservation and stability of AMPs by encapsulation
2.3 AMPs stability in formulated products
2.4 Stability of AMPs within solid matrices
2.5 Fiber formation to preserve AMPs
2.6 Packaging mechanisms and conditions for AMPs
3 Case studies: Use of peptides in pharmaceutical and cosmeceutical products
3.1 General outline regarding conservation and packaging in pharmaceutical and cosmetics industries
3.2 Cosmeceutical topical cream
3.3 Pharmaceutical topical cream
4 Conclusions
References
Chapter 17 Synthetic peptides quality control and assurance
Abstract
Keywords
1 Introduction
2 Quality building
2.1 Characterization
2.2 Good laboratory practices
2.3 Process parameters, quality attributes, and risk analysis matrix
3 Quality control
4 Quality assurance
4.1 Personnel
4.2 Materials and suppliers
4.3 Equipment
4.4 Facilities
4.5 Methods and document management system
4.6 Metrics and measures
5 Quality management
5.1 Quality planning
5.2 Improvement
5.3 Relationship management
5.4 Quality management system
References
Index

Luis H. Reyes

Luis H. Reyes is an Associate Professor at Universidad de Los Andes (Bogotá, Colombia) and Director of the Product and Process Design Group. Luis is a chemical engineer (Universidad Industrial de Santander, Colombia) with a PhD. in Chemical Engineering from Texas A&M University (College Station, TX, USA). His research interest focuses on applying biological engineering to design and develop bioprocesses and bioproducts using various tools borrowed from the natural sciences, such as molecular and synthetic biology, reverse engineering of microorganisms, laboratory adaptive evolution, and microbiology. He teams with an interdisciplinary research group in the biomedical engineering area to develop bionanoconjugated vehicles to transport and deliver biological molecules with therapeutic potential, including gene and enzyme replacement therapies. He also works in the discovery and production of peptides with applications in the medical, food, and petrochemical industries. In food engineering, Luis studies the sensory design of beer and the protein replacement of dairy products.

Affiliations and expertise

Associate Professor, Universidad de Los Andes, Colombia

Juan C. Cruz

Juan Carlos Cruz obtained his undergraduate degree in Chemical Engineering from the National University of Colombia (2002) and later his Ph.D. in Chemical Engineering from Kansas State University (KSU) (2010) for his work on a new platform for enzyme immobilization to address biocatalysis challenges in non-aqueous media. Cruz has experience as Head of New Product Development in a chemical company, where he developed several nanotechnological applications to improve critical attributes of plastics according to the requirements and standards of new market niches. In 2016, he joined the Department of Biomedical Engineering at Universidad de Los Andes (Bogotá, Colombia). Cruz has more than fifteen years of working in the fields of industrial and medical biotechnology and, in particular, in the development of nanobiocatalysts, the fundamental understanding of protein-protein, protein-surface, and protein-lipid interactions, the development of new nanoparticulate vehicles for the release and guidance of pharmacological molecules and the search for unique peptides with membrane activity.

Affiliations and expertise

Universidad de Los Andes, Colombia

Gregory R. Wiedman

Gregory R. Wiedman works at Seton Hall University in NJ, USA.

Affiliations and expertise

Seton Hall University, NJ, USA

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Antimicrobial Peptides

A Roadmap for Accelerating Discovery and Development

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Luis H. Reyes

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