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Solid-Phase Peptide Synthesis The Merrifield Method

SOLID-PHASE PEPTIDE SYNTHESIS THE MERRIFIELD METHOD... [Pg.1141]

Solid-Phase Peptide Synthesis The Merrifield Method... [Pg.1141]

Current practice of the conventional solid phase peptide synthesis (the Merrifield method) is based largely on the use of polystyrene and poly-dimethylacrylamide supports (see Fig. 17). The latter polymer was introduced in the 1970s [12,133 to provide a relatively more polar support, as compared with polystyrene. However, accumulation of experimental evidoice since then (ct Rrf. 70), indicates that an ideal polyn r support for SPPS should be comi tible with both polar (H-bonding) and nonpolar (hydrophobic) residues on the peptic grafts (Fig. 17). When the polymer support is not compatible with the growing peptide grafts, phase separation occurs, and the synthesis becomes inefficient or impracticable. [Pg.28]

First we shall consider reactions for traditional chemical synthesis of peptides and then we look at reactions used in automated solid-phase peptide synthesis. The method for solid-phase peptide synthesis was invented by R. B. Merrifield (Rockefeller University), for which he earned the 1984 Nobel Prize in Chemistry. Solid-phase p>eptide synthesis reactions are so reliable that they have been incorporated into machines called peptide synthesizers (Section 24.7D). [Pg.820]

We shall now exemplify the solid-phase peptide synthesis approach by c )c/o-[-L-Val-[)-Pro-D-Val-L-Pro-]], which was prepared by Merrifield himself, the inventor of the method (B.F. Gisin, 1972). [Pg.235]

Merrifield method See solid phase peptide synthesis Meso stereoisomer (Section 7 11) An achiral molecule that has chirality centers The most common kind of meso com pound IS a molecule with two chirality centers and a plane of symmetry... [Pg.1288]

Automated Peptide Synthesis The Merrifield Solid-Phase Method 1037... [Pg.1037]

The novel concept of synthesizing a molecule while attached to a swollen cross-linked resin bead was introduced and demonstrated by R. B. Merrifield with the solid-phase peptide synthesis method about 20 years ago (1,2). The procedure involves the covalent attachment of an amino-acid residue to the polymer bead followed by the addition of subsequent amino-acid units in a stepwise manner under conditions that do not disrupt the attachment to the support. At the completion of the assembly of the peptide, the product is cleaved from the resin and recovered. The macro-scopically insoluble support provides convenient containment of the desired product so that isolation and purification from soluble co-products in the synthesis can be achieved by simple... [Pg.501]

In preparing these various libraries, extensive use is made of solid phase synthetic methods. These methods are all derived from the solid phase peptide synthesis (SPPS) method developed by Merrifield in 1963. When performing a large number of syntheses, it is preferable to perform the synthetic steps on a solid bead rather than completing the entire synthesis in the solution phase. The solid-phase technique makes byproduct removal and final compound purification easier. The organic chemistry literature contains a wealth of different types of solid-phase supports and novel linkers for attaching the synthetic substrate to the bead. [Pg.124]

Solid-phase peptide synthesis does not solve all purification problems, however. Even if every coupling step in the ribonuclease synthesis proceeded in 99% yield, the product would be contaminated with many different peptides containing 123 amino acids, 122 amino acids, and so on. Thus, Merrifield and Gutte s six weeks of synthesis was followed by four months spent in purifying the final product. The technique has since been refined to the point that yields at the 99% level and greater are achieved with current instrumentation, and thousands of peptides and peptide analogs have been prepared by the solid-phase method. [Pg.1149]

The major disadvantage of solid-phase peptide synthesis is the fact that all the by-products attached to the resin can only be removed at the final stages of synthesis. Another problem is the relatively low local concentration of peptide which can be obtained on the polymer, and this limits the turnover of all other educts. Preparation of large quantities (> 1 g) is therefore difficult. Thirdly, the racemization-safe methods for acid activation, e.g. with azides, are too mild (= slow) for solid-phase synthesis. For these reasons the convenient Merrifield procedures are quite generally used for syntheses of small peptides, whereas for larger polypeptides many research groups adhere to classic solution methods and purification after each condensation step (F.M. Finn, 1976). [Pg.237]

Without doubt, the solid-phase peptide synthesis (Merrifield method) remains a preferred method for controlling all five critical molecular design parameters (size, shape, topology, flexibility, and surface chemistry) by precisely producing amino-acid sequences in a stepwise fashion. The scope and limitations of this approach have been reviewed [34] and widely recognized [35]. These solid-phase syntheses with protection/deprotection procedures are used routinely to produce numerous, previously unattainable [36], polypeptides and polynucleotides. One of the ultimate synthetic efforts in the control of CMDPs was the total synthesis by Khorana et al. [37] of a DNA molecule in the 1960s. [Pg.207]

Several syntheses of the peptide have been reported by solution methods (74-76). After the introduction of solid-phase peptide synthesis, Marshall and Merrifield conducted the first study of the synthesis of the peptide by using the new technique (77). A -Boc chemistry was used, and Merrifield resin was selected as the solid support. The side chain protections were as follows His, Arg, and Asp were protected by Bn groups Arg by a NO2 group. The Phe was esterified onto the resin in ethanol with the presence of 1 equivalent of triethylamine. The symmetric anhydride method was used for the coupling of the amino acids, and DCC was the coupling reagent. The following cycle of reactions was used to introduce each new residue (Table 7) ... [Pg.2196]

There are two general approaches to the synthesis of peptides the classical method, in which all reactions are carried out in homogeneous solution, and the solid phase method, in which the reactions are heterogeneous ones between soluble reagents and an insoluble peptide chain that is attached to a solid support. Since its introduction by Merrifield in 1962 solid-phase peptide synthesis has been applied successfully to the preparation of a great number and variety of peptides including proteins [1,2]. [Pg.547]


See other pages where Solid-Phase Peptide Synthesis The Merrifield Method is mentioned: [Pg.241]    [Pg.131]    [Pg.247]    [Pg.28]    [Pg.1242]    [Pg.289]    [Pg.183]    [Pg.230]    [Pg.214]    [Pg.41]    [Pg.193]    [Pg.1185]    [Pg.591]    [Pg.121]    [Pg.121]    [Pg.131]    [Pg.168]    [Pg.3]    [Pg.2198]   


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