Peptide Synthesis Flashcards
what are natural peptides commonly used as and give examples?
signalling molecules + substrates
- peptide hormones - LH, prolactin, GH, insulin, vasopressin, oxytocin, cholecystokinin
- neurotransmitters + neuropeptides
- snake, ant, spider venoms
- toxins from microbes + aquatic life
give examples of some peptides + peptidomimetics in clinical use?
- goserelin (prostate cancer)
- saquinavir (HIV/AIDS)
- gramicidin (antibacterial)
- insulin (diabetes)
- interferons
why do we synthesise peptides + analogues?
investigate biological systems + biochem pathways
inhibit/change pathways
improve on nature -> higher potency, greater specificity
condensation reactions are not …. useful
synthetically
describe block protection briefly?
- block amine of aa1
- block acid of aa2
- condense using dehydrating agent
how do carbodiimides work?
- protonated carbodiimides = v electrophilic
- adduct contains good leaving group
- urea bi-prod = v stable + precipitates from solution
give examples of protecting groups?
- amino protecting groups (N protection)
- carboxyl protecting groups
- solid phase peptide synthesis
- side chain protecting groups
- orthogonal protection strategies
describe N protection briefly?
- need to make N non-nucleophilic
- remove lone pair availability
what are the most common N-protecting groups?
carbamates
what does the choice of carbamate depend on?
functional group sensitivity
when would you use Boc?
acid sensitive
protected amino acid (tertiarybutyloxycarbonyl)
when would you use Cbz?
reduction sensitive
protected amino acid (benzyloxycarbonyl)
when would you use Fmoc?
base sensitive
protected amino acid
fluorenyloxycarbonyl
what is the most common reagent in boc protection?
di-tert-butyldicarbonate
boc anhydride
what is the source of Cbz?
benzyloxycarbonyl chloride
when is Cbz protection unsuitable?
for Cys, Met, Lys
if R1 = H, what is the product in Cbz protection?
Cbz - Gly
what is the source of Fmoc?
succinimidyl ester because = good leaving group
if R1 = H, what is the product in Fmoc protection?
Fmoc-Gly
why are mild bases used in Fmoc protection?
strong bases cause racemisation of AA
end up with 1:1 mix of D and L isomers
get peptides with non-natural stereoisomers = inactive
if you have a methyl/ethyl group, what do u hydrolyse with?
hydroxide
if you have a tertiary butyl group, what do u hydrolyse with?
TFA
if you have a benzyl group, what do you hydrolyse with?
hydrogenate
what are the advantages of SPPS?
- automation
- rapid + reliable
- easy purification: wash beads
- cheap
- many different applications
