Synthesis of peptide thioesters via an N-S acyl shift reaction under mild acidic conditions on an N-4,5-dimethoxy-2-mercaptobenzyl auxiliary group.
An efficient method of peptide thioester synthesis is described. The reaction is based on an N-4,5-dimethoxy-2-mercaptobenzyl (Dmmb) auxiliary-assisted N-S acyl shift reaction after assembling a peptide chain by Fmoc-solid phase peptide synthesis. The Dmmb-assisted N-S acyl shift reaction proceeded efficiently under mildly acidic conditions, and the peptide thioester was obtained by treating the resulting S-peptide with sodium 2-mercaptoethanesulfonate. No detectable epimerization of the amino acid residue adjacent to the thioester moiety in the case of Leu was found. The reactions were also amenable to the on-resin preparation of peptide thioesters. The utility was demonstrated by the synthesis of a 41-mer peptide thioester, a phosphorylated peptide thioester and a 33-mer peptide thioester containing a trimethylated lysine residue.
Nakamura
Ken'ichiroh
K
Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
Kanao
Tomoki
T
Uesugi
Tomoya
T
Hara
Toshiaki
T
Sato
Takeshi
T
Kawakami
Toru
T
Aimoto
Saburo
S
D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D014269:Trifluoroacetic Acid / Q000737:chemistry
D004952:Esters; D010455:Peptides; D013438:Sulfhydryl Compounds; D014269:Trifluoroacetic Acid