title: Synthesis of N-acetylglucosaminyl asparagine-substituted puromycin analogues.
abstract: As part of our project aimed to introduce specifically glycosylated amino acids into proteins, new glycosylated puromycin analogues were chemically synthesized. Introduction of a free N-acetylglucosaminyl asparaginyl side chain abolished the activity of puromycin completely, but when the sugar OH groups were rendered increasingly hydrophobic by acetylation or benzylation, up to 8% of the activity was recovered. The results of our preliminary inhibition tests suggest that the interaction of puromycin analogues and therefore also of glycosylated aminoacyl tRNA, with the ribosomal A site increase with hydrophobicity of the modifying protecting groups.
authors.affiliation: Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
authors.forename: P
authors.initials: P
authors.lastname: Kirsch
authors.forename: N
authors.initials: N
authors.lastname: Kusunose
authors.forename: J
authors.initials: J
authors.lastname: Aikawa
authors.forename: T
authors.initials: T
authors.lastname: Kigawa
authors.forename: S
authors.initials: S
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Ogawa
mesh_terms: D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011500:Protein Synthesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011691:Puromycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D012346:RNA, Transfer, Amino Acyl; C000009:N-acetylglucosaminylasparagine; D011691:Puromycin; D000117:Acetylglucosamine