固相合成基础 SPPS

2．

Name: Aminomethyl polystyrene Resin Category: Resins

3．（用于合成肽醇）

Name: DHP HM Resin

Category: Resins

4．

Name: HMPA-AM Resin Category: Resins

5．（用于合成肽酰胺）

Name: Knorr

Resin

Category: Resins

6．（用于合成肽酰胺）

Name: Knorr-2-Chlorotrityl Resin

Category: Resins

7．

Name: MBHA Resin Category: Resins

8．

Name: Merrifield Resin Category: Resins

9．

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Name: Rink

amide-AM Resin Category: Resins

10．

Name: Rink amide-MBHA Resin

Category: Resins

11．

Name: Sieber Resin Category: Resins

12

Name: Wang Resin Category: Resins

13．（用于合成肽醛）

Name: Weinreb AM Resin

Category: Resins

七、Overview of Peptide Synthesis

Introduction

Proteins are present in every living cell and possess a variety of biochemical activities. They appear as enzymes, hormones, antibiotics, and receptors. They compose a major portion of muscle, hair, and skin. Consequently, scientists have been very interested in synthesizing them in the laboratory. This interest has developed into a major synthetic field known as Peptide Synthesis. The major objectives in this field are four-fold:

1. To verify the structure of naturally occurring peptides as determined by degradation techniques.

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2. To study the relationship between structure and activity of biologically active protein and

peptides and establish their molecular mechanisms.

3. To synthesize peptides that are of medical importance such as hormones and vaccines. 4. To develop new peptide-based immunogens.

Solid Phase Peptide Synthesis (SPPS)

The fundamental premise of this technique involves the incorporation of N-?-amino acids into a peptide of any desired sequence with one end of the sequence remaining attached to a solid support matrix. While the peptide is being synthesized usually by stepwise methods, all soluble reagents can be removed from the peptide-solid support matrix by filtration and washed away at the end of each coupling step. After the desired sequence of amino acids has been obtained, the peptide can be removed from the polymeric support.

The general scheme for solid phase peptide synthesis is outlined in Figure 1. The solid support is a synthetic polymer that bears reactive groups such as -OH. These groups are made so that they can react easily with the carboxyl group of an N-?-protected amino acid, thereby covalently binding it to the polymer. The amino protecting group (X) can then be removed and a second N-?-protected amino acid can be coupled to the attached amino acid. These steps are repeated until the desired sequence is obtained. At the end of the synthesis, a different reagent is applied to cleave the bond between the C-terminal amino acid and the polymer support; the peptide then goes into solution and can be obtained from the solution.

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Fmoc Strategy in SPPS

The crucial link in any polypeptide chain is the amide bond, which is formed by the condensation of an amine group of one amino acid and a carboxyl group of another. Generally, an amino acid consists of a central carbon atom (called the ?-carbon) that is attached to four other groups: a hydrogen, an amino group, a carboxyl group, and a side chain group. The side chain group, designated R, defines the different structures of amino acids. Certain side chains contain functional groups that can interfere with the formation of the amide bond. Therefore, it is important to mask the functional groups of the amino acid side chain.

The general scheme which outlines the strategy of Fmoc synthesis is shown in Figure 2. Initially, the first Fmoc amino acid is attached to an insoluble support resin via an acid labile linker. Deprotection of Fmoc, is accomplished by treatment of the amino acid with a base, usually piperidine. The second Fmoc amino acid is coupled utilizing a pre-activated species or in situ activation. After the desired peptide is synthesized, the resin bound peptide is deprotected and detached from the solid support via TFA cleavage.

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