Work of Robert Bruce MerriField

7/28/2019 Work of Robert Bruce MerriField

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WORKOFROBERTBRUICEMERRIFIELD

Presented by: Sudheer1

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Born July, 15 1934

Died May ,14 2006

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

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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 groupN.N Dicyclohexylcarbodiamide (DCC)

HF in CH3COOH for breaking ester linkage

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i) Deprotection of N protected amino acid by treating with

CF3COOHR

(CH3)3C-O-CO-NHCHCOOH (CH3)3C=CH2 + CO2

R

BOC + H2N-CH-COOH

CF3COOH

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ii)DCC a dehydrating agent helps in removal of H2O between

COOH and NH2

R1 R2BOC-NHCHCOOH + HNHCHCOOCH2

+ C6H11N=C=NC6H11

(DCC)

R1 R2

BOC-NHCHCONHCHCOOCH2+

C6H11 NHCONH C6H11

(Urea)

Polymer

resin

Polymer

resin

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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

R1

BOC NHCHCOOH + ClCH2

R1

BOCNHCHCOOCH2

Polymer

resin

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

i)CF3COOH

ii) Washing

HNHCHCOOCH2

Polymer

Resin

R1BOCNHCHCOOCH2

R1

Polymer

resin

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Step III- Another N-terminal protected amino acid is added in the

prescence of DCC (N.N-dicyclohexylcarbodiamide).

R2 R1BOCNHCHCOOH + HNHCHCOOCH

2

DCC

R2 R1

BOCNHCHCONHCHCOOCH2

i)CF3COOH

ii) Washing

R2 R1

HNHCHCONHCHCOOCH2

Polymer

resin

Polymer

resin

Polymer

resin

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R3 R2 R1

BOCNHCHCOOH + HNHCHCONHCHCOOCH2

DCC

R3 R2 R1

BOCNHCHCONHCHCONHCHCOOCH2

Polymerresin

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 R1BOCNHCHCONHCHCONHCHCOOCH2

HF

R3 R2 R1

HNHCHCONHCHCONHCHCOOH

Polymer

resin

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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!

3/12/2012

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Work of Robert Bruce MerriField

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