인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
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지원사업
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커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Aspergillus flavipes L-methionine γ-lyase (MGL) has been authenticated as a powerful anticancer agent towards various solid tumors, however, the catalytic efficiency and stability of this enzyme remains the main challenge for its further in vivo applications. Thus, the objective of this study was to enhance the catalytic efficiency, structural stability of A. flavipes MGL, in addition to boost their anticancer activity, via conjugation with β-cyclodextrin. The purified A. flavipes MGL was (38.1 μmol/mg/min) was conjugated with β-cyclodextrin, with immobilization yield 80%. The conjugation process of MGL with β-cyclodextrin was verified from the FTIR analysis, molecular docking analysis, ensuring the covalent conjugation process via the hydrogen, and hydrophobic interactions with the cyclodextrin hydroxyl groups and MGL surface amino acids residues. The free and CD-MGL have the same optimum reaction temperature 37 °C, reaction pH 7.5 and pH stability pH 6.5-8.0. The CD-MGL conjugates had a significant stability to proteinase K and trypsin digestion. The affinity of CD-MGL was increased by ~ 2 folds to L-methionine (K<sub>M</sub> 3.1 mM), compared to the free one (K<sub>M</sub> 7.2 mM), as well as the catalytic efficiency of MGL was increased by 1.8 folds upon cyclodextrin conjugation. The higher affinity of CD-MGL for L-methionine might be due to re-orientation of the MGL to bind with the substrate by multiple interactions hydrogen, hydrophobic and covalent bonds compared to the free one. The thermal stability of MGL was increased by ~ 2 folds for the tested treatments, upon cyclodextrin conjugation. The in vitro anticancer activity of CD-MGL was enhanced by 2 folds against the HCT-116 (IC<sub>50</sub> value 13.9 μmol/mg/min) and MCF7 (IC<sub>50</sub> value 9.6 μmol/mg/min), compared to the free MGL (~ 21.4 μmol/mg/min). The enzymes displayed a significant activity against the proliferation of Ehrlich ascites carcinoma in vivo, with an obvious improvement on the liver tissues, as revealed from the histopathological sections.
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