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)

B3072	B3168	B3150
B3167	B3669	F0305
F0507	F0505	F0506
F0772	F0293	F0294
F0295	F0296	F0508
F0297	F0669	F0298
F0653	F0652	F0752
F0299

Condensing Agents, Activating Agents & Deprotecting Agents

B1774

E0901

H0468

After-treatment Agents

A0492	B0041	B1087
B0991	C0401	D3479
D0944	D0970	E0032
E0143	I0021	M0093
M0097	M0346	P1610
T0191	T0662	T0431
T1533

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

A1861	B1774	B1651
B1657	B1658	B1213
C0119	C1988	C1676
C1408	C1639	C1651
C0903	C1379	C1375
C0793	D0436	D0437
D3262	C1242	D2039
D0254	D2919	D4029
D1601	D2159	C1415
D1672	D2201	D1114
D1662	E0363	E0901
E0219	F0726	H0468
H1208	H0528	H0395
B0249	N0220	N0634
O0200	P0919	T2821
T2224

Protecting Agents

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