Solid phase peptide synthesis in water VI: evaluation of water-soluble coupling reagents for solid phase peptide synthesis in aqueous media.
Solid phase peptide synthesis requires large amounts of organic solvents, the safe disposal of which is an important environmental issue. Peptide synthesis, if performed in water and using less or nontoxic reagents, circumvents the disposal problem. Our ultimate aim is to develop an "environment-friendly" solid phase peptide synthesis (SPPS) methodology. Previously, we showed that SPPS in water is feasible. To perform SPPS in water, the coupling reagent must be water-soluble and maintain its reactivity in water. For this report, we tested the efficacy of the water-soluble coupling reagents, 2-(5-norbornene-2,3-dicarboximido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), towards SPPS in water. We successfully synthesized Leu-enkephalin amide on a solid support suspended in aqueous 50% EtOH using DMT-MM and 2-(4-sulfophenylsulfonyl)ethoxycarbonylamino acids.
Faculty of Pharmaceutical Sciences, Kobe Gakuin University, Ikawadani-cho, Nishi-ku, Kobe 651-2180, Japan.
Keiko
K
Hojo
Mitsuko
M
Maeda
Naoko
N
Tanakamaru
Kayo
K
Mochida
Koichi
K
Kawasaki
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides / Q000737:chemistry*; D000431:Ethanol; D005782:Gels; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry*; D009861:Onium Compounds / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
C511853:2-(5-norbornene-2,3-dicarboximido)-1,1,3,3-tetramethyluronim; C467606:4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride; D003497:Cyclic N-Oxides; D005782:Gels; D009025:Morpholines; D009861:Onium Compounds; D010455:Peptides; D012997:Solvents; D014867:Water; D000431:Ethanol