Lecture 10 Flashcards
What is the first reason that enzyme catalyzed condensation reactions to form polypeptides only works in Nature?
-2 different amino acids can be connected four different ways; The enzyme is regioselective and gives only one of the four products–in lab you would end up getting ~ equal amounts of all 4 possible products instead
What is the second reason amide synthesis by condensation isn’t viable in the laboratory?
- Because of the proton transfer reaction that takes place when a carboxylic acid is mixed with an amine
- Nu attack cannot occur for the salt because the ammonium ion does not he a lone pair of electrons and because the negative charge makes the carboxylate ion a poor substrate for nucleophilic attack
How can the proton transfer problem be fixed?
By activating the carboxyl group with DCC
What is the problem with DCC mediated coupling reactions?
No selectivity; Two Amino Acids will give ~ equal amounts of all four possible dipeptides
How can the selectivity problem be fixed?
By protecting the amino group of one AA and the carboxyl group of the other.
-Selective coupling is followed by deprotection at both ends of the product
How is amino group protected?
As a carbamate. (Draw a carbamate right now)
What does a carbamate do?
-electron withdrawing group; diminishes the reactivity of the nitrogen atom by bringing the lone pair into conjugation with the carbamate carbonyl group
Commercial reagent available for installing “t-boc” protecting group?
Di-tert-butyl dicarbonate (t-boc)2O
-Draw this + t-boc as a protecting group right now
How do you remove t-boc?
-Can be removed under many different conditions
How do you remove CBz protecting group?
Catalytic Hydrogenation
-Reagents H2 over Pd/C
Two different amino protecting groups
1) t-boc. comes from (t-boc)2O costs 125$/100g
- Easily removed in high yield under many different conditions
2) CBz. comes from Benzyl Chloroformate costs 70$/100g
- Stable in acidic conditions–removed by catalytic hydrogenation
How are carboxyl groups protected?
Esterification
-usually done as either methyl ester or benzyl ester
Four steps of peptide synthesis
1) Protect the NH2 group of one amino acid
2) Protect the carboxyl group of the other amino acid
3) Couple the protected amino acids with DCC
4) remove the protecting groups
Ribonucleases
Small enzymes that cut RNA into pieces
Hemoglobin
-2,336 amino acid residues divided into four polypeptide chains
