Test 4 Peptide Synthesis Flashcards
three letter and single letter codes for amino acids
know these
Basic strategies for peptide synthesis
Reactants → Protection → Activation → Synthesis
→ Deprotection
What are the blocking groups to protect alpha amino groups?
- Boc
- Fmoc
What are the blocking groups to protect alpha carboxyl groups?
- for SPPS: polystyrene / resin
- for solution: protected as an alkyl or aryl ester
What are amino groups converted into?
- alkoxycarbonylamino derivatives
- made up of amides and esters which leads to the inactivity
What is the Z group?
when an H at the amino group is converted into a Benzyloxycarbonyl group to protect it
How do you remove the Z group?
- synthesize Z group and peptide under basic conditions
- remove Z group under acidic conditions
- add Carbamic acid which spontaneously decarboxylates and gives back the amino group
What is Boc?
- amino group protector
- t-Butoxycarbonyl (Boc) protection
- more labile to acids than Z group
What is Fmoc?
- amino group protector
- 9-Fluorenylmethoxycarbonyl (Fmoc) protection
- stable under acidic conditions; cleaved under basic conditions
- deprotected with piperidine
What are protecting groups for alpha-amino?
Benzyloxycarbonyl (Z-)
What are protecting groups for epsilon-amino (Lys)?
t-Butoxycarbonyl (Boc-)
What are protecting groups for alpha-carboxyl?
Methyl, ethyl
What are protecting groups for B-Sulfhydryl (Cys)?
Benzyl (-SBzl)
What are protecting groups for Beta-OH (Ser, Thr)?
t-Butyl
What are protecting groups for Phenolic OH (Tyr)?
Benzyl
What does activation of the carboxyl end result in?
amides
How do you activate the carboxyl end?
convert it to an anhydride
What are conditions for ideal peptide synthesis?
- peptide bond formation must be rapid and quantitative under mild conditions
- absence of side reactions
- does not challenge the integrity of adjacent chiral centers
- co-products should be easily removed
What is DCCI?
- activating (coupling) agent for the carboxyl end to make the amide bond
- before the amide bond is formed, the intermediate formed is: O-acylisourea
What is another way to activate the carboxyl group if you don’t want to use DCCI?
use active esters
Pepsyn K
modified polyacrylamides type gel
Expansin
modified polyacrylamides type gel
Tentagel
- modified polyether chain
- maintains good flow rates in columns
What are handles, linkers, or spacers used for?
- used to modify properties of polymeric supports to keep the PS bond intact (the bond between the resin and aa)
PAM resin
- PAM between the resin and the aa as a handle / linker
- esp. useful when using Boc as a protecting group
