Efficient solid phase peptide synthesis. Use of methanesulfonic acid alpha-amino deprotecting procedure and new coupling reagent, 2-(benzotriazol-1-yl)oxy-1,3-dimethylimidazolidinium hexafluorophosphate (BOI).
An efficient method for solid phase peptide synthesis was developed, which consists of N alpha-selective deprotection by dilute methanesulfonic acid, in situ neutralization and rapid coupling reaction using benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) or 2-(benzotriazol-1-yl)oxy-1,3- dimethylimidazolidinium hexafluorophosphate (BOI) reagent. Selective removal of the N alpha-Boc group by dilute methanesulfonic acid was of more advantage than removal by TFA in terms of stability of semipermanent protecting groups and suppression of undesired side reactions. The use of in situ neutralization and rapid coupling method reduced intramolecular aminolytic cyclization by shortening exposure of the deprotected nucleophilic amino group. A successful synthesis of porcine brain natriuretic peptide (pBNP) has been achieved using this efficient solid phase peptide synthesis scheme.
Kiso
Y
Y
Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Japan.
Fujiwara
Y
Y
Kimura
T
T
Nishitani
A
A
Akaji
K
K
D000595:Amino Acid Sequence; D000818:Animals; D005563:Formic Acid Esters / Q000737:chemistry; D007093:Imidazoles; D007202:Indicators and Reagents; D008698:Mesylates; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000138:chemical synthesis; D010455:Peptides / Q000138:chemical synthesis*; D013552:Swine; D014230:Triazoles
D005563:Formic Acid Esters; D007093:Imidazoles; D007202:Indicators and Reagents; D008698:Mesylates; D009419:Nerve Tissue Proteins; D010455:Peptides; D014230:Triazoles; C000345:t-butyloxycarbonyl group; D020097:Natriuretic Peptide, Brain; C078987:2-(benzotriazol-1-yl)oxy-1,3-dimethylimidazolidinium; C045880:methanesulfonic acid