Peptides as Drugs. Discovery and Development

  • ID: 2179881
  • Book
  • 242 Pages
  • John Wiley and Sons Ltd
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By covering the full spectrum of topics relevant to peptide drugs, this timely handbook serves as an introductory reference for both drug developers and biomedical researchers interested in pharmaceutically active peptides, presenting both the advantages and challenges associated with this molecular class.

The first part discusses current approaches to developing pharmaceutically active peptides, including case studies of the use of peptidic drugs in cancer and AIDS therapy. The second part surveys strategies for the development and targeting of peptidic drugs.

With its integration of biochemical, pharmaceutical and clinical research, this work reveals the full picture of modern peptide drug research in a single volume, making it an invaluable reference for medicinal chemists, biochemists, biotechnologists, and those in the pharmaceutical and biotechnological industries.

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PEPTIDES AS DRUGS: DISCOVERY AND DEVELOPMENT

Discovery of New Potential Drug Targets and the Limitations of Druggability

Protein Interaction Domains are at the Core of Signaling Pathways

Peptides as Inhibitors of Protein Interactions

MIMICS OF GROWTH FACTORS AND CYTOKINES

Introduction

The Cytokines

Defining Receptor Recognition Sites in Cytokines Using Chimeric Proteins

Receptor Recognition Sites are Organized as Exchangeable Modules

The Concept of Fusing the Cytokine to the Soluble Receptor: Hyper–IL–6

Antagonists Specifically Inhibiting IL–6 Trans–Signaling

In Vitro Evolution of Peptides and Proteins

PEPTIDES DERIVED FROM EXON v& OF THE CD$$ EXTRACELLULAR DOMAIN PREVENT ACTIVATION OF RECEPTOR TYROSINE KINASE AND SUBSEQUENTLY ANGIOGENESIS AND METASTATIC SPREAD OF TUMOR CELLS

Introduction

CD44 Proteins and Their Involvement in RTK Activation

CD44v6 Acts as a Coreceptor for c–Met and Ron

Three Amino Acids in CD44 Exon v6 are Crucial for the CD44v6 Coreceptor Function, and Small Peptides Can Interfere with This Function

The Ectodomain of CD44v6 Binds to HGF

Peptides Corresponding to Exon v6 of CD44 Inhibit Metastatic Spread of Tumor Cells

The Significance of the Collaboration Between CD44v6 and c–Met In Vivo

The CD44v6 Peptides Interfere with Angiogenesis

PEPTIDE APTAMERS TARGETING THE VIRAL E6 ONCOPROTEIN INDUCE APOPTOSIS IN HPV–POSITIVE CANCER CELLS

Human Papillomaviruses and Oncogenesis

Peptide Aptamers Targeting the HPV E6 Oncoprotein

E6–Targeting Peptide Aptamers: Therapeutic Perspectives

Perspectives

THE PREVENTION OF HIV INFECTION WITH VIRAL ENTRY INHIBITORS

Introduction: The Potential of Peptides as Drugs in the Treatment of HIV Infection

The HIV Entry Process

Peptides that Inhibit Receptor or Coreceptor Binding

Inhibitors of the Viral and Cellular Membrane Fusion Process

Entry Inhibitory Peptides Selected by the Phage Display Technology

Limitations of Peptides it the Treatment of HIV Infection

Strategies to Prolong the In Vivo Half–Life of Antiviral Peptides

Antiviral Peptides in Gene Therapy of HIV Infection

INTRACELLULAR EXPRESSION OF PEPTIDES

Introduction

Peptide Design and Expression Cassettes

Stable Delivery and Expression of Peptides: Gamma–Retro– and Lentiviral Vectors

Gamma–Retroviral Vectors

Lentiviral Peptide Delivery

Vectors for Transient Expression of Peptides: Adenoviruses and Adeno–Associated Viruses

Perspective

THE INTERNALIZATION MECHANISMS AND BIOACTIVITY OF THE CELL–PENETRATING PEPTIDES

Introduction

Discovery and Classification of CPPs

Internalization Mechanisms of Cell–Penetrating Peptides

Models of CPP Uptake

The Current View of CPP Uptake

CPPs as Cargo Delivery Vehicles

Delivery of Proteins

CPPs in Gene Delivery

Delivery of Oligonucleotides

Cytotoxicity of Cell–Penetrating Peptides

In Vivo Drug Delivery with CPPs

CPPs for Targeted Delivery

PRODUCTION AND PURIFICATION OF MONOMERIC RECOMBINANT PEPTIDE APTAMERS: REQUIREMENTS FOR EFFICIENT INTRACELLULAR UPTAKE AND TARGET INHIBITION

Introduction

Protein Production

Protein Purification

Isolation of Monomeric, Natively Folded Proteins

Increasing Peptide Production, Purification and Efficacy by Using Scaffolds

The Use of Cell–Penetrating Peptides for Cellular Uptake of Purified Proteins

Classification of Therapeutic Peptides

Production and Administration of Therapeutic Peptides In Vivo

PEPTIDE ARRAYS ON SOLID SUUPORTS: A TOOL FOR THE IDENTIFICATION OF PEPTIDE LIGANDS

Introduction

Synthesis of Peptide Arrays

Applications of Peptide Arrays

Challenges in High–Throughput Screening (HTS)

Future Perspectives

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Bernd Groner
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