Toshiyuki Kosaka

Convolutamides A ∼ F, novel γ-lactam alkaloids from the marine bryozoan Amathia convoluta

Abstract Convolutamides A ∼ F, new alkaloids containing an N-acyl-γ-lactam moiety with a dibromophenol group, have been isolated from the Floridian bryozoan Amathia convoluta and the structures elucidated on the basis of spectroscopic data.

Novel Isozyme-Specific Quantitation Method for Alpha-Amylases inHuman Plasma Revealed Possible AMY2B Induction by Alpha-AmylaseInhibitor, CS-1036

In a clinical trial of an α-amylase inhibitor (CS-1036), which was developed for the treatment of patients with type 2 diabetes, the half-life of plasma CS-1036 concentration was prolonged with the increase of the dose level. The prolonged half-life was assumed to be associated with alternation in the plasma level of any one of the α-amylase isozymes from the treatment. Human α-amylase is classified into 3 isozymes encoded by AMY1A, AMY2A, and AMY2B. Due to high sequence homology between α-amylase isozymes and the low plasma level, it is extremely challenging to quantify individual isozymes. A mass spectrometry-based approach, Multiple Reaction Monitoring (MRM) using the Absolute Quantification (AQUA) strategy, has been applied to quantification of target proteins, and this approach provides high selectivity and specificity. Here we report a novel quantitation method of α-amylase isozymes, which is a combination of purification of α-amylase from plasma by starch affinity adsorption and LCMRM- MS. This method was applied to the plasma samples from the clinical trial of CS-1036. As a result, only AMY2B showed a statistically significant increase in a time-dependent manner. This result suggested that AMY2B might be related to the prolonged half-life of CS-1036.