Synthesis of nocistatin C-terminal and it’s amide derivatives as an opioid peptide

Abstract

A new biological active hexapeptide of C-terminal of nocistatin, contains Glu-Gln-Lys-Gln-Leu-Gln sequence was synthesized according to solid phase peptide synthesis on the surface of 2-chloro tritylchloride resin and using fmoc-protected amino acids in the presence of TBTU (O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyl uranium tetrafluoroborate) as a coupling reagent. Then, amidation of the C-terminus of peptides was carried out using NH4Cl and alkyl ammonium chloride (RNH3Cl) in the presence of TBTU and a tertiary amine (DIPEA) as the base at room temperature in good to high yields. Cleavage of the desired peptides from the surface of the resin after the addition of TFA (1%) provided the protected peptides. All of the products were purified using preparative HPLC and structures were assigned according to MALDI-mass spectrometry data.