Powerful solvent systems useful for synthesis of sparingly-soluble peptides in solution.
Our maximum protection strategy for the synthesis of human parathyroid hormone(1-84) indicates that fully protected peptide segments in the form of Boc-peptide phenacyl (Pac) ester are relatively soluble in ordinary organic solvents such as DMF, NMP or DMSO, which are suitable for coupling segments. However, about 1% of such segments synthesized were found to be insoluble even in the most polar solvent, DMSO. Thus, a more powerful solvent which can be used for their peptide synthesis was pursued. Among the solvent systems tested, a mixture of trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) and trichloromethane (TCM) or dichloromethane (DCM) was found to be most powerful for dissolving such sparingly-soluble protected peptides. These solvent systems were confirmed to be useful for the removal reaction of the carboxy-terminal Pac esters from the sparingly-soluble segments. They were then tested for the coupling reactions of fully protected Boc-peptides with other sparingly-soluble peptide esters. The TFE/TCM or TFE/DCM system was extremely useful for coupling segments without danger of racemization and of trifluoroester formation, if WSCI was used as the coupling reagent in the presence of 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine (HOOBt).
Kuroda
H
H
Peptide Institute Inc., Protein Research Foundation, Osaka, Japan.
Chen
Y N
YN
Kimura
T
T
Sakakibara
S
S
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D009320:Atrial Natriuretic Factor / Q000138:chemical synthesis; D004952:Esters; D005563:Formic Acid Esters / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis*; D011994:Recombinant Proteins / Q000138:chemical synthesis; D012995:Solubility; D012996:Solutions; D012997:Solvents; D013237:Stereoisomerism
D000596:Amino Acids; D004952:Esters; D005563:Formic Acid Esters; D010455:Peptides; D011994:Recombinant Proteins; D012996:Solutions; D012997:Solvents; C000345:t-butyloxycarbonyl group; D009320:Atrial Natriuretic Factor