The course is mainly focused on the design and synthesis of Peptides. Understand the concepts of protection and deprotection reactions and coupling. To design the synthetic route for Peptidomimetics and heterocycle tethered peptides. Aimed to understand analytical characterization and interpretation of data for peptides and peptidomimetics.
Course Outcomes
- Can synthesise the protected amino acids
- Able to design the synthetic strategy for the coupling of amino acids and peptides with different protections.
- Able to deduce the scheme for synthesising the peptidomimetics.
- Interpret the data and solve the structure of the peptide/mimetic
Contents
Module: 1 (9 hours)
- Basics of amino acids and peptides
- Biological importance of peptides
- Classification of amino acids, peptides,
- Synthesis and structure of amino acids, peptide bond formation
- Protecting groups (N-terminus, C-terminus, and side chain),
- Deprotection strategies
- Coupling methods
Module: 2 (9 hours)
- New generation coupling agents
- Cleavage of the peptide bond by chemical and enzymatic methods
- Amino acid Sequencing
- Racemization in peptide synthesis.
- Solution and solid phase techniques.
- Applications of peptides (peptide-based vaccines, peptide pharmaceuticals, peptide drug delivery systems)
- Hands on training for the synthesis of protected amino acids
Module: 3 (9 hours)
- Design and synthesis di, tri and tetrapeptides
- Peptidomimetics-Introduction and examples
- Design and synthesis of peptidomimetics.
- Biological activities of heterocycle tethered peptidomimetics.
- Peptidomimetics pertaining to (side-chain, main-chain, combined side-chain& main-chain modified peptides)
- Hands on training for the synthesis of di and tripeptides and deprotections
Module: 4 (9 hours)
- Solid phase peptide synthesis-introduction.
- Use of resins and resin bound reagents.
- Applications of SPPS
- Selection of resin for the SPPS
- Isolation and purification of peptides
- Characterization of peptides an mimetics and interpretation of the analytical data
- Hands on training for the design and synthesis of peptidomimetics
Textbooks & Supporting Literature
- Jenssen, H.; Hamill, P.; Hancock, R.E. Peptide antimicrobial agents. Clin. Microbiol. Rev. 2006, 19, 491–511.
- Wimley, W.C. Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem. Biol. 2010, 5, 905–917.
- Wang, G. Database-guided discovery of potent peptides to combat hiv-1 or superbugs. Pharmaceuticals (Basel) 2013, 6, 728–758.
- Wang, G. Structures of human host defense cathelicidin ll-37 and its smallest antimicrobial peptide kr-12 in lipid micelles. J. Biol. Chem. 2008, 283, 32637–32643.
- Powers, J.P.; Rozek, A.; Hancock, R.E. Structure-activity relationships for the beta-hairpin cationic antimicrobial peptide polyphemusin i. Biochim. Biophys. Acta 2004, 1698, 239–250.
- Rozek, A.; Friedrich, C.L.; Hancock, R.E. Structure of the bovine antimicrobial peptide indolicidin bound to dodecylphosphocholine and sodium dodecyl sulfate micelles. Biochemistry 2000, 39, 15765–15774
References
Selsted, M.E.; Harwig, S.S.; Ganz, T.; Schilling, J.W.; Lehrer, R.I. Primary structures of three human neutrophil defensins. J. Clin. Investig. 1985, 76, 1436–1439.
Ganz, T. Defensins: Antimicrobial peptides of innate immunity. Nature Rev. Immunol. 2003, 3, 710–720.
Bowdish, D.M.; Davidson, D.J.; Hancock, R.E. Immunomodulatory properties of defensins and cathelicidins. Curr. Top. Microbiol. Immunol. 2006, 306, 27–66.
