Synthesis of N-acetylglucosaminyl asparagine-substituted puromycin analogues.
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.
Kirsch
P
P
Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Kusunose
N
N
Aikawa
J
J
Kigawa
T
T
Yokoyama
S
S
Ogawa
T
T
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
D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D012346:RNA, Transfer, Amino Acyl; C000009:N-acetylglucosaminylasparagine; D011691:Puromycin; D000117:Acetylglucosamine