Solid Phase Peptide Synthesis (SPPS)
Solid phase synthesis is a process in which synthetic reactions are carried out on a solid support. The idea was developed by R .B. Merrifield to synthesise polypeptides and this work earned him the Nobel Prize in 1984. Solid phase synthesis can be used in many ways for example to create carbohydrates, peptides and oligonucleotides. I will be looking at solid phase peptide synthesis.
A peptide is when two amino acids are joined together resulting in the loss of a water (H2O) molecule. The resulting C-N bond between the two amino acids is referred to as a peptide bond. When a large number of amino acids are joined together by peptide bonds (polypeptide chains) they can form proteins. Proteins are present in every living cell and they have a variety of uses as they can be enzymes, hormones, antibiotics and receptors.
In this experiment I will be forming a cyclic dipeptide, where the ends of the peptide are joined together. Dipeptides are used in everyday living. An example of a dipeptide that may be used in daily life is Aspartame which is an artificial sweetener. There are many areas of importance for synthetic peptides. A few examples are stated below: To chemists as the ultimate proof of the structure of natural products, To biochemists as models for studying the specificity and mechanism of action enzymes, To physical chemists as models for the investigation of protein conformation, To pharmacologists as sources of products with modified or selective hormonal activity, To immunologists as tools for defining and understanding immunological specificity. There are also many high profile uses of peptides in drug design, chemotherapy and immunology e.g.
In diagnostics with the preparation on mono and polyclonal antibodies.
As hormones for therapeutic agents.
In receptor characterisations and isolation
For clarification in enzyme-peptide substrate interactions
As inhibitors of proteolytic enzymes.
And the major objectives in the field on peptide synthesis are 1.
To verify the structure of naturally occurring peptides as determined by degradation techniques. 2.
To study the relationship between structure and activity of biologically active protein and peptides and establish their molecular mechanisms. 3.
To synthesise peptides that are of medical importance such as hormones and vaccines. 4.
To develop new peptide-based immunogens.
R. B. Merrifield pioneered Solid phase peptide synthesis as a way of simplifying and accelerating the process of peptide synthesis so that the synthesis of long peptides would be more practical and that so as development continues it may be automated. The revolutionary premise of solid phase peptide synthesis is that a peptide can be formed with any desired amino acid sequence but the peptide is anchored to an insoluble support at one end of the peptide chain. Once the required peptide has been formed the insoluble support can be cleaved away with a reagent that will liberate the peptide into solution. All the reactions involved are brought to 100% completion and this is done with the use of excess reagents, which allows the reactions to proceed to completion in the minimum time and results in faster synthesis and so a homogeneous product can be obtained. One of the advantages of this method of solid phase peptide synthesis is that the arduous purification steps that are involved in the synthesis of the peptide are eliminated and are replaced with simple washing and filtration of the solid. The entire process of solid phase peptide synthesis can be carried out in only one suitably designed vessel so that the transfer of materials from one container to another is cut out of the process. Basic outline
There are synthetic polymers that have a reactive (X) group. These groups are made to react with the carboxyl group of an amino acid so the amino acid is covalently bonded to the polymer. During this step the amine group of the...
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