Peptides are chains of amino acid residues connected via amide linkages. Peptides composed up to 10 amino acid residues are referred to small peptides, while those with up to 100 residues are known as (poly)peptides. A peptide moiety forms prime constituent of not only proteins but also aspartame, an artificial non-saccharide sweetener. Peptides serve various functions in organisms, especially the peptide hormones which play important roles in signal transductions. Some synthetic peptides can also be used as reagents for biochemical research and in pharmacy.¹⁾
Since the number of naturally occurring bioactive peptides is limited and the genes corresponding to the peptides are usually unknown, peptide synthesis enables the further research for functional analysis of the peptides. To date, peptides with several dozen of residues can be obtained by solid phase peptide synthesis. Peptides with a small number of residues can also be prepared in a large scale by liquid phase synthesis. This section shows reagents used in peptide synthesis.

●Solid Phase Peptide Synthesis
Two popular synthetic methods have been developed: Boc (t-Butoxycarbonyl) and Fmoc (9-Fluorenylmethoxycarbonyl) methods. Fmoc methods are preferred due to milder condition required for the removal of the protective groups as compared to the Boc method and simpler procedure for the cleavage of peptides from resins.²⁾

Sequential condensation reactions are followed by cleavage from the resin and removal of protective groups with cleavage cocktail and subsequently precipitation by methanol. The residue is generally further purified by HPLC to obtain the desired peptide.

【Reagents】
•Resin (preload type: C-terminus of the Fmoc-amino acid is linked)
•Fmoc-amino acids (Protection of the side chain is recommended)
•Condensation agent: 1H-Hydroxybenzotriazol-1-yloxytripyrrolidinophosphonium Hexafluorophosphate
•Activating Agent: 1-Hydroxybenzotriazole
•Solvent: N,N-Dimethylformamide (low water content is preferable)
•Deprotecting Agent: Piperidine
•Cleavage cocktail (for removal from the resin and deprotection of the side-chain) :
Trifluoroacetic acid, reducing agents (depending upon the residues)

Fmoc-Amino Acids (Side Chain Protected Type)

Condensing Agents, Activating Agents & Deprotecting Agents

After-treatment Agents

Fmoc-Amino Acids (Side Chain Protected Type)

B3150	B3167	F0669
F0305	F0294	F0295
F0296	F0297	F0298
F0299	F0652	F0293
F0507	F0508	F0505
F0506	F0653	B3072
B3168

Condensing Agents, Activating Agents & Deprotecting Agents

B1774

P0453

T1243

After-treatment Agents

E0032	D0944	D3479
E0143	M0097	B0991
T0191	T0431

For other amino acids, please refer to the Section “Amino Acids”.

Amino Acids

●Liquid Phase Peptide Synthesis
As in the case usual organic synthetic methods, liquid phase peptide synthesis is performed by the condensation of protected amino acids with condensation agents by a batch technique.³⁾ The condensation is followed by work-up and purification and the resulting peptide is subjected to further condensation with another amino acid. The choice of condensation and activation agents as well as protective groups depends on the intended purpose. Protecting agents for synthesis of protected amino acids which are not commercially available are also illustrated in this section.⁴⁾

Condensing Agents

Protecting Agents

Condensing Agents

C0119	O0200	C1379
C1375	C0793	E0363
D1601	H1208	B1774
B1651	D1114	N0634
C1408	C1639	C1651
C0903	C1676	D2039
D3262	T1673	D2201
D2919	N0220	B1213
D1662	C1242	D2159
C1415	D1672	F0726
D0436	D0437	D0254
T2224	E0219	H0528
H0395	B0249	C1988
A1861	B1657	B1658
P0919

Protecting Agents

B1969	D1463	B0988
B1089	N0363	F0197
B3021	C0176	C1591
C1574	D1547	D3878
D3879	D3880	P1277
P1281	C1131	C1124
C0683	B0916	F0239
C0933