Synthesis of beta-(S-methyl)thioaspartic acid and derivatives.
Beta-(S-Methyl)thioaspartic acid occurs as a posttranslational modification at position 88 in Escherichia coli ribosomal protein S12, a position that is a mutational hotspot resulting in both antibiotic-resistant and antibiotic-sensitive phenotypes. Critical to research designed to determine the biological function of beta-(S-methyl)thioaspartic acid will be the availability of synthetic beta-(S-methyl)thioaspartic acid as well as derivatives designed for peptide incorporation. We report here the synthesis of beta-(S-methyl)thioaspartic acid and derivatives. The installation of the beta-methylthio moiety into the aspartic acid structure was accomplished by electrophilic sulfenylation of N-protected-l-aspartic acid derivatives with 2,4-dinitrophenyl methyl disulfide. Following this key transformation, we were able to prepare protected beta-(S-methyl)thioaspartic acid derivative suitable for peptide coupling.
Heredia-Moya
Jorge
J
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, DHHS, Bethesda, MD 20892, USA.
Kirk
Kenneth L
KL
D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D004952:Esters; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D012335:RNA, Ribosomal / Q000737:chemistry; D012269:Ribosomal Proteins / Q000737:chemistry* / Q000378:metabolism
D029968:Escherichia coli Proteins; D004952:Esters; D010455:Peptides; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; C034212:ribosomal protein S12; C018934:3-methylaspartic acid; D001224:Aspartic Acid