Peptide therapeutics Flashcards
What are the main advantages of peptide therapies over small molecules and biologics?
Peptides combine favorable properties of small molecules (stability, permeability) and biologics (specificity, low immunogenicity). They are selective, potent, and break down into non-toxic amino acids.
How does solid-phase peptide synthesis (SPPS) work?
SPPS involves anchoring a growing peptide chain to a solid resin. Amino acids are added stepwise (C → N direction), protected by Fmoc groups. Steps include coupling (amide bond formation), deprotection, and cleavage.
What are some common peptide modifications and their purposes?
- PEGylation: Increases circulation time.
- Cyclisation: Enhances protease resistance.
- Lipidation: Improves serum binding.
- Stapling: Stabilizes α-helical structures.
What is phage display, and how is it used?
Phage display encodes peptides in bacteriophage genomes, displaying them on the phage surface. Peptides that bind targets are identified through sequencing after selection rounds.
How do antimicrobial peptides (AMPs) kill bacteria?
AMPs disrupt bacterial membranes (e.g., pore formation via barrel-stave or toroidal models) or inhibit cell wall biosynthesis (e.g., lipid II sequestration by vancomycin).
What makes AMPs less prone to resistance development?
AMPs target fundamental components like membranes or lipid intermediates, which require large-scale changes for resistance. This contrasts with single-point mutations conferring resistance to many small molecules.
Describe the discovery of teixobactin.
Discovered in 2015 using iChip technology, teixobactin targets lipid I, lipid II, and C55-PP. It has shown no resistance development in initial studies, highlighting its clinical potential.
