Piperidine Azasugars Displaying Competitive α-Rhamnosidase Inhibition and their Kinetic Mechanism

• Published in: Applied biological chemistry Vol. 54; no. 6; pp. 881 - 888
• Main Authors: Cho, J.K., Gyeongsang National University, Jinju, Republic of Korea, Rengasamy, Rajesh, Gyeongsang National University, Jinju, Republic of Korea, Curtis-Long, Marcus John, Brandeis University, South Street Waltham, MA, USA, Kim, J.H., National Academy of Agricultural Science, RDA, Suwon, Republic of Korea, Lee, J.W., Gyeongsang National University, Jinju, Republic of Korea, Park, K.H., Gyeongsang National University, Jinju, Republic of Korea
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01.12.2011; Springer Nature B.V; 한국응용생명화학회
• Subjects: Alanine; alpha-rhamnosidase; Applied Microbiology; Bioactive Materials; Biological Techniques; Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; competitive inhibition; Enantiomers; INHIBICION; INHIBITION; L-Alanine; L-Rhamnose; L-Serine; Piperidine; piperidine azasugars; Rhamnose; time-dependent; 농학; time-dependent; α-rhamnosidase; competitive inhibition; piperidine azasugars
• ISSN: 1738-2203; 2468-0834; 2234-344X; 2468-0842
• DOI: 10.1007/BF03253176

Azasugars derived from L-alanine and L-serine were screened for inhibitory activity against α-rhamnosidase. The enantiomers of 1,6-dideoxynojirimycin (ent-1,6-dDNJ) (1) and (2S,3R)-2-(hydroxymethyl)piperidin-3-ol (5) showed highly specific and potent inhibition against α-rhamnosidase with K∧i values of 4.2 and 16.6 μM, respectively. Structure of the best inhibitor features the same stereochemical configuration as L-rhamnose at C2, C3, and C4 centers. In kinetic studies, both compounds exhibited competitive inhibition behavior. Compound 1 manifested simple reversible slow-binding inhibition with the following kinetic parameters: k₃= 1.17 nM-¹ min-¹, k₄= 5.96×10-³ min-¹, and K∧i∨app=5.1 mM.