Solid-phase peptide synthesis and agent for use in such synthesis

1. A method of synthesizing a target peptide having the following structure:

X—AA 1 —AA 2 . . . AA n —Y,

wherein,

AA is an L or D amino acid residue,

X is hydrogen or an amino protective group,

Y is OH or NH 2 , and

n is an integer greater than about 2 and less than about 60;

said method comprising:

a. coupling a pre-sequence peptide to a support, wherein said pre-sequence peptide comprises from about 3 to about 9 amino acid residues having side chain functionalities which are, protected during the synthesis, wherein each of the amino acid residues has a propensity factor P α >0.57 and a propensity factor P β ≦1.10,

b. coupling one or more N-α-protected amino acids to the N-terminus of the pre-sequence peptide or to a cleavable linker attached to the N-terminus of the pre-sequence peptide to form said target peptide, wherein each coupling is performed in stepwise fashion and under conditions in which each of the amino acids of the target peptide is coupled and subsequently N-α-de-protected; wherein the pre-sequence peptide reduces or eliminates propensity of the target peptide to adopt a β-sheet structure during the coupling and increases the coupling efficiency during the synthesis of the target peptide in comparison to the synthesis of the target peptide prepared under the same conditions without said pre-sequence peptide; and

c. cleaving said target peptide from said pre-sequence peptide.

2. The method of claim 1 , wherein the pre-sequence peptide is enzymatically cleaved from said target peptide.

3. The method of claim 1 , wherein the pre-sequence peptide comprises amino acid residues that lack propensity to adopt the β-sheet structure.

4. The method of claim 1 , wherein the method further comprises removing the N-α-protective group from the target peptide before step (c).

5. The method of claim 1 , wherein the method further comprises at least one of the following steps: inserting a first linker between the target peptide and the pre-sequence peptide, and inserting a second linker between the pre-sequence peptide and the support.

6. The method of claim 5 , wherein step (c) further comprises cleaving the first linker, the second linker or both the first and second linkers to produce the target peptide.

7. The method of claim 1 , wherein said pre-sequence peptide consists of from 5 to 7 amino acid residues.

8. The method of claim 1 , wherein said pre-sequence peptide consists of a polylysine.

9. The method of claim 8 , wherein said pre-sequence peptide consists of -(Lys) 6 -.

10. The method of claim 1 , wherein the yield or purity of the target peptide is increased in comparison to the synthesis of the target peptide prepared under the same conditions without said pre-sequence peptide.