Solid-phase Peptide Synthesis

Harm-Anton Klok

Solid-phase peptide synthesis (SPPS), first introduced by R. B. Merrifield [1], involves a repeated sequence of a-amino acid coupling and deprotection reactions performed on an insoluble solid support [2]. The support enables the use of excess a-amino acids and reagents, which helps to drive each of the reactions to completion. By-products and excess reagents are easily removed by filtration. After attachment of the last a-amino acid the linker connecting the support and the peptide, and protective groups that mask the side-chains of trifunctional a-amino acids, are cleaved, affording the crude product. Because of incomplete reactions, side-reactions, or impure reagents, the crude product usually contains defect sequences and other contaminants; these are usually removed by high-performance liquid chromatography (HPLC).


(i) DIPEA/CH2Cl2

(i) TFA/CH2Cl2

(ii) HF/anisole


Scheme B.25.1.



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