CHM3930 Lecture Notes - Lecture 5: Side Chain, Tethering, Tangled
20 Jun 2018
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Week 5 -SPPS (T3)
Solid phase peptide synthesis
Tethering peptide in one spot and growing from N-terminus
Linker used to: ***IN EXAM
oAttach the peptide to the solid phase
oSupply the functionality at the c-terminus
Leaves a carboxylic acid (Oxygen taken from the linker)
Could leave a C-terminal amide (useful in some cases)
Protecting groups
oFmoc -amine protecting group (***REMEMBER STRUCTURE FOR EXAM)
Combination of amide and ester -carbamate (HN-C(=O)O)
Fmoc Deprotection mechanism
oExposed to a 20% solution of piperidine in dimethylformamide (DMF)
DMF =polar aprotic solvent -likes to behave like water
oAim is to expose NH group attached to Fmoc group
oPiperidine NH is basic and attacks H in middle of Fmoc group
Aromatic rings adjacent to H can stabilise the resulting charge
opiperidine abstracts the distant H
oProduct: amine that you want + carbon dioxide + di benzo fulvene (?)
oAmine wants proton -takes it from piperidine
oTo get amide on its own, CO2 bubbles off (gas) and di benzo fulvene can be
filtered/rinsed out (loose molecule, everything needed is attached to solid phase)
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Tethering peptide in one spot and growing from n-terminus. Linker used to: ***in exam: attach the peptide to the solid phase, supply the functionality at the c-terminus. Leaves a carboxylic acid (oxygen taken from the linker) Could leave a c-terminal amide (useful in some cases) Protecting groups: fmoc -amine protecting group (***remember structure for exam) Fmoc deprotection mechanism: exposed to a 20% solution of piperidine in dimethylformamide (dmf) Dmf =polar aprotic solvent -likes to behave like water: aim is to expose nh group attached to fmoc group, piperidine nh is basic and attacks h in middle of fmoc group. Resin cleavage: cleave off with harsh acid, side chain protecting groups come off with the resin (solid phase, if mild acid only protecting groups will fall off -protein will remain attached to resin, highly reactive cations are generated. Need to be removed/trapped with nucleophilic scavengers .
