Synthesis and evaluation of novel photoreactive alpha-amino acid analog carrying acidic and cleavable functions.
A novel photoreactive alpha-amino acid bearing an acidic residue and a cleavable diazirine was developed. To mimic common acidic alpha-amino acids, the residue was designed to be N-acylsulfonamide that possesses an acidic proton and is able to dissociate under the physiological conditions. The inhibition assay of its biotin-tagged derivative with glutamyl endopeptidase from Staphylococcus aureus V8 strain revealed a Ki(app) value of 162 microM, which is slightly higher than the K(m) value of a common substrate. Upon UV irradiation, this derivative specifically photolabeled glutamyl endopeptidase, L-glutamate dehydrogenase, glutamic oxalacetic transaminase, and L-glutamine synthetase, all the enzymes exhibit high affinity toward acidic alpha-amino acids. In addition, N-acylsulfonamide group functioned as a cleavable linker in mild basic solution after a brief N-alkylation. Either the multifunctional nature or the simple structure of this acidic alpha-amino acid surrogate would be useful as versatile photoreactive building block.
Bongo
Nlandu B
NB
Laboratory of Biorecognition Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan.
Tomohiro
Takenori
T
Hatanaka
Yasumaru
Y
D000596:Amino Acids / Q000737:chemistry* / Q000528:radiation effects; D019921:Biotinylation; D010777:Photochemistry / Q000379:methods*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000201:enzymology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology; D014466:Ultraviolet Rays
D000596:Amino Acids; D011480:Protease Inhibitors; D013449:Sulfonamides; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase