WORK OF

ROBERT BRUICE MERRIFIELD

Presented by: Sudheer

3/12/2012

American biochemist Born in Fort Worth, Texas Was awarded Nobel prize in the year 1984 for his work on solid phase synthesis Completed his education from university of California

Born July, 15 1934 Died May ,14 2006

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The important components involved in a solid phase peptide synthesis are

A solid phase Protecting group Tert butyl oxy carbonyl group ( BOC) Dehydrating group N.N Dicyclohexylcarbodiamide (DCC) HF in CH3COOH for breaking ester linkage

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i) Deprotection of N protected amino acid by treating with CF3COOH R (CH3)3C-O-CO-NHCHCOOH CF3COOH (CH3)3C=CH2 + CO2 R BOC + H2N-CH-COOH

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ii)DCC a dehydrating agent helps in removal of H2O between COOH and NH2 R1 R2 Polymer BOC-NHCHCOOH + HNHCHCOOCH2 resin + C6H11N=C=NC6H11 (DCC)

R1 R2 BOC-NHCHCONHCHCOOCH2
+

Polymer resin

C6H11 NHCONH C6H11 (Urea)

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R3 R2 R1 HNHCHCONHCHCONHCHCOOH N terminal end C terminal end

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Step I-The N terminal acid is protected by BOC group and added to the chloromethylated polymer. The amino acid gets attached to the polymer by the ester bond formed between COOH group and CH2Cl of the polymer

BOC

R1 NHCHCOOH + ClCH2

Polymer resin

R1 BOCNHCHCOOCH2

Polymer resin

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Step II- The protecting group (BOC) is then removed from first amino acid by treatment with trifluoro acetic acid. The resin is then washed with organic solvents R1 BOCNHCHCOOCH2
i)CF3COOH
Polymer Resin

R1

ii) Washing
Polymer resin

HNHCHCOOCH2

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Step III- Another N-terminal protected amino acid is added in the prescence of DCC (N.N-dicyclohexylcarbodiamide). R2 R1 Polymer BOCNHCHCOOH + HNHCHCOOCH2
resin

DCC
R2 R1 BOCNHCHCONHCHCOOCH2 i)CF3COOH ii) Washing
Polymer resin

R2 R1 HNHCHCONHCHCOOCH2
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Polymer resin
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R3 R2 R1 BOCNHCHCOOH + HNHCHCONHCHCOOCH2 DCC R3 R2 R1 BOCNHCHCONHCHCONHCHCOOCH2

Polymer resin

Polymer resin

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Step IV- The synthesized polypeptide is removed from the solid support by breaking the ester linkage by the action of HF R3 R2 R1 BOCNHCHCONHCHCONHCHCOOCH2 HF

Polymer resin

R3 R2 R1 HNHCHCONHCHCONHCHCOOH

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Advantages of this method are : It gives very high yield of polypeptide. Less time consuming. Accurate sequence of amino acids

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BIBLIOGRAPHY
Organic chemistry- John McMurry 5th edition pg 1096-1098 Organic chemistry Paula Bruice 4th edition pg 980-981

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Thank

You!
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