Question

1. Draw an “arrow-pushing' mechanism for carbodiimide activation of a carboxylic acid for amine addition. 2. What is a peptide-nucleic acid (PNA) and why is it useful? 3. What side chains are protected by trityl in solid phase peptide synthesis? 4. What side chains are protected by PMC (2,2,5,7,8-pentamethylchroman-6-sulphonyl) in solid phase synthesis? 5. What are the practical limits of peptide and DNA solid phase synthesis (how many monomers in each) and why is this a limitation?

Answer 1

1. Carbodimide
General formula: RN=C=NR
Reaction: Addition of amines to carboxylic acids in the presence of cabodimides to form amides.
Mechanism:

1 - HN-R' N=C=N HN-R' RENHAR - NH "OH Mechanism: + HA=c=N + - 7 N = = N carbodimide R R - ( carboscylic acid NH - R N-R" O-acylisourea intermediate

The O-acylisourea formed may further react through three pathways.


ro R-NH2 NAR R Reaction pathway 1 Oy 2 Pathway 2 Rearrangement N -R" o-acylisourea O NH OH ou N-R"

2. Peptide nucleic acids (PNA) are syntheic polymer which have many applications in microbiology.
The structure resemble the natural nucleic acids (DNA and RNA) in living being.
The backbone of the polymer comprises of repeating units of N-(2-aminoethyl)-glycine connected through peptide linkages. There are purine and pyrimide bases are attached to chain through methyl bridges and carbonyl group.
It is used in the treatment of viral, bacterial and parasitc ailments and also for treatment of certain cancers.
3. In solid phase peptide synthesis (spps) it is important to protect the side chains to avoid other recations to compete with the main polymerization reactions. The side chains containing hydroxyl groups are protected by the trityl.