5 Peptide and Protein Lecture Flashcards
Describe the various applications of Peptides and Proteins (PPs) in the field of medicine.
Peptides and Proteins (PPs) are utilized in therapeutics enzymatic or regulatory activity, replacing deficient proteins, augmenting pathways, providing novel functions, targeting specific activities, interfering with molecules, delivering compounds, developing vaccines, and diagnosing diseases.
Explain the advantages of using Peptides and Proteins (PPs) as pharmaceuticals in comparison to small molecules.
PPs offer highly complex functions that small molecules cannot mimic, exhibit high specificity with minimal interference in normal physiological processes, are naturally produced and well-tolerated, serve as effective replacement therapy, have faster clinical development, and provide unique form and function for extensive patent protection.
Discuss the limitations of Peptides and Proteins (PPs) as pharmaceuticals and how these challenges are being addressed in the field of medicine.
PPs face challenges such as wide therapeutic dose ranges, difficulty in production from human plasma or animal sources, differences from functional human molecules, immunogenic potential, and variability in immunological responses. Advances in recombinant DNA, protein engineering, and tissue culture techniques have enabled commercial-scale production, resemblance to endogenous molecules, and reduced immunological responses.
How are Peptides and Proteins (PPs) used in protein vaccines, and what are the specific examples of diseases they can help prevent or treat?
PPs are utilized in protein vaccines to protect against foreign agents like HPV and HepB, treat autoimmune diseases such as Rh (D) immunization, and combat cancer through anti-her2 therapy. They play a crucial role in immune response modulation and disease prevention.
Define the role of Peptides and Proteins (PPs) in protein diagnostics and how they contribute to clinical decision-making in healthcare settings.
PPs are essential in protein diagnostics as they assist in clinical decision-making by detecting specific biomarkers, monitoring disease progression, and guiding treatment strategies. Their high specificity and diverse functions make them valuable tools in personalized medicine and precision healthcare.
Describe the challenges in drug delivery for peptides and proteins, focusing on formulation issues and delivery issues.
Peptides and proteins face challenges in drug delivery due to formulation issues like low solubility, degradation by GI enzymes, and poor membrane permeability. Delivery issues include the need for parenteral administration, invasive methods, and limited bioavailability from subcutaneous space.
How does the low systemic availability of peptides and proteins impact their oral administration?
Peptides and proteins have low systemic availability when administered orally due to factors like low solubility, degradation by GI enzymes, poor membrane permeability, large first-pass metabolism, opsonisation, and conformational changes.
Define the concept of depot-based formulations in drug delivery for peptides and proteins.
Depot-based formulations in drug delivery for peptides and proteins involve formulations that decrease dosing frequency by creating a reservoir of the drug at the injection site, allowing for sustained release and potentially improving patient compliance.
Describe the bioavailability range and advantages of subcutaneous delivery for injectable biologics.
Subcutaneous delivery of injectable biologics offers a bioavailability range of 50-80% and advantages like better patient acceptance, compliance, and convenience for self-administration compared to intravenous methods. Depot-based formulations can also decrease dosing frequency.
What are the absorption kinetics challenges faced by peptides and proteins in subcutaneous delivery?
Absorption kinetics challenges in subcutaneous delivery for peptides and proteins include physical barriers like structural proteins of the extracellular matrix, limited injectable volume versus therapeutic amount needed, and low bioavailability due to interactions with ECM components, immune cells, and foreign body responses.
Describe the challenges associated alternative ‘patient-friendly’ routes like peroral, transdermal/subcutaneous, and transmucosal for drug delivery. What are the barriers to these routes?
Alternative ‘patient-friendly’ routes for drug delivery face challenges such as enzymatic and physicochemical barriers. Enzymatic barriers include proteolytic enzymes like endopeptidases and exopeptidases. Physicochemical barriers stem from the physiology and histology of mucosal membranes, hindering permeation of large molecules.
How do proteolytic enzymes break down peptides and proteins in drug delivery? What are the two main classes of proteolytic enzymes and their functions?
Proteolytic enzymes break down peptides and proteins by cleaving them at internal or external bonds. The two main classes are endopeptidases (e.g., chymotrypsin, trypsin) that cleave internal bonds, and exopeptidases (e.g., carboxypeptidases) that cleave external bonds.
Define protease superfamilies and explain their occurrence in drug delivery. Which major protease superfamilies exist and where are they found in the body?
Protease superfamilies like serine, cysteine, metallo, and aspartyl play a role in drug delivery. They occur in various locations such as the stomach (pepsin), GI luminal enzymes, pancreatic proteases, brush-border membrane, cytosol, portal blood, and liver.
How can peptides be rendered resistant to proteolytic attack in drug delivery? Explain the methods used to achieve this resistance.
Peptides can be made resistant to proteolytic attack in drug delivery by co-administering protease inhibitors, substituting (L) amino acids with (D) amino acids, incorporating non-cleavable peptide bond isosteres, or through cyclisation or PEGylation.
Discuss the occurrence and functions of proteolytic enzymes like pepsin, enteropeptidase, and liver enzymes in drug delivery. Where are these enzymes found and what are their roles?
Proteolytic enzymes like pepsin occur in the stomach, enteropeptidase in the brush-border membrane, and liver enzymes (ALT, AST, ALP, GGT) in the liver. They play roles in breaking down peptides, activating enzymes, and maintaining metabolic functions.
