• Applied Biological Chemistry
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• 제51권3호
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• pp.171-176
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• 2008

기질 화합물로써 3${\beta}$-Hydroxy-12-oleanen-28-oic acid 유도체(1-30)들과 그들의 protein tyrosine phosphatase(PTP)-1B 저해활성에 관한 비교분자 유사성 지수분석(CoMSIA)보델을 유도하였다. QSAR 모델의 통계 값은 CoMFA>CoMSIA${\geq}$HQSAR>2D-QSAR 모델의 순서로 양호하였다. 최적화된 CoMSIA F1 모델은 grid 3.0${\AA}$과 field fit 정렬조건에서 가장 족은 예측성과 상관성($r^2_{cf}$=0.754 및 $r^2_{ncv}$=0.976)을 나타내었다. 저해 활성에 관한 CoMSIA상의 기여비율(%)은 수소결합 받게장(48.9%), 입체장(25.8%) 및 소수성장(25.4%)의 순서이었다. 그러므로 기질 화합물의 PTP-1B에 대한 저해활성은 $R_4$-치환기의 수소결합 받게 장(A)에 의존적이었다. 등고도 분석 결과로부터 $R_1$-치환기는 수소결합 받게장이 작고 $R_3$-치환기는 입체장이 작으며 그리고 $R_4$-치환기는 수소결합 받게장, 소수성 및 입체장이 큰 치환기가 저해활성을 증가시킬 것으로 예측되었다.

• Applied Biological Chemistry
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• 제42권3호
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• pp.252-255
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• 1999

Chalcones 유도체들을 합성하고 farnesyl protein transferase(FPTase) 저해활성을 측정하여, 기질분자의 치환기 변화에 따른 구조와 활성과의관계(SAR)를 Free-Wilson법과 Hansch법으로 검토하였다. Benzoyl group 중 X-치환기가 styryl중 Y-치환기보다 활성에 더욱 큰 영향을 미쳤으며 meta- > ortho-, para-치환기의 순으로 활성을 나타내었다. 또한, X및 Y-치환기의 소수성이 적정값$(({\Sigma}logP)_{opt}\;=\;3.915)$에 근접할수록 활성이 증가 하였으며, X-치환기의 입체효과와(Es > O) 전자밀게 Y-치환기에 의한 공명효과(R < O)가 활성에 미치는 중요한 요소로 인식되었다. 다루어진 화합물중에서 비 치환체, 8은 가장 높은 FPTase저해활성$(pl_{50}\;=\;4.30)$을 나타내었다. 그리고 기질 수용체간의 상호작용을 가정하여 제안하였다.

• BMB Reports
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• 제34권3호
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• pp.268-273
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• 2001

In addition to the recognition site for glutamate, the N-methyl-D-aspartate (NMDA)-preferring glutamate receptor subtype shows a binding site for glycine. In this paper, we present the effects of 3-(4,6-dichloro-2-carboxymethylamino-5,7-dichloroquinoline-2-carboxylic acid (MDL 29951), a potent inhibitor of glycine binding to the NMDA receptor, on glutamate dehydrogenase (GDH) from bovine brains. The incubation of GDH isoproteins from bovine brains with MDL 29951 resulted in a dose-dependent loss of enzyme activity Separately or together, 2-oxoglutarate and NADH did not give an efficient protection against the inhibition, indicating that GDH isoproteins saturated with NADH or 2-oxoglutarate are still open to attack by MDL 29951. MDL 29951 was an uncompetitive inhibitor with respect to both 2-oxoglutarate and NADH for GDH isoproteins. These results suggest that the binding site of MDL 29951 is not directly located at the catalytic site, and the inhibition of GDH isoproteins by MDL 29951 is probably due to a steric hindrance, or a conformational change altered upon the interaction of the enzyme with its inhibitor. The inhibitory effects of MDL 29951 on GDH isoproteins were significantly diminished in the presence of ADP. GDH I reacted more sensitively with ADP than GDH II on the inhibition by MDL 29951. Our results suggest a possibility that the two types of GDHs are differently regulated by MDL 29951, depending on the physiological concentrations of ADP.

• BMB Reports
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• 제31권5호
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• pp.459-467
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• 1998

A new set of functional group interaction energy descriptors relevant to the ACE (Angiotensin-Converting Enzyme) inhibitory peptide, QSAR (Quantitative Structure Activity Relationships), is presented. The functional group interaction energies approximate the charged interactions and distances between functional groups in molecules. The effective energies of the computationally derived geometries are useful parameters for deriving 3D-QSAR models, especially in the absence of experimentally known active site conformation. ACE is a regulatory zinc protease in the renin-angiotensin system. Therapeutic inhibition of this enzyme has proven to be a very effective treatment for the management of hypertension. The non bond interaction energy values among functional groups of six-feature of ACE inhibitory peptides were used as descriptor terms and analyzed for multivariate correlation with ACE inhibition activity. The functional group interaction energy descriptors used in the regression analysis were obtained by a series of inhibitor structures derived from molecular mechanics and semi-empirical calculations. The descriptors calculated using electrostatic and steric fields from the precisely defined functional group were sufficient to explain the biological activity of inhibitor. Application of the descriptors to the inhibition of ACE indicates that the derived QSAR has good predicting ability and provides insight into the mechanism of enzyme inhibition. The method, functional group interaction energy analysis, is expected to be applicable to predict enzyme inhibitory activity of the rationally designed inhibitors.

• Bulletin of the Korean Chemical Society
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• 제13권5호
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• pp.565-570
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• 1992

The 1,5-sigmatropic rearrangements involving group (X) migration in ${\omega}$(X)-substituted 1,3-pentadiene, $C^1H_2=C^2H-C^3H=C^4H-C^5H_2-X$, where X = H, $CH_3$, $BH_2$, $NH_2$, OH or F, are investigated MO theoretically using the AM1 method. For the migrating groups without lone pair electrons, X = H, $CH_3$, or $BH_2$, the suprafacial pathway is favored, whereas for the migrating groups with lone pair electrons participating in the TS, $X=NH_2$, OH, or F, the antarafacial pathway is favored electronically. However excessive steric inhibition in the antarafacial TS for $X=NH_2$ leads to subjacent orbital controlled suprafacial process. The antarafacial shift of F is relatively disfavored compared to that of OH due to smaller orbital overlap and larger interfrontier energy gap in the TS.

• Bulletin of the Korean Chemical Society
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• 제31권5호
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• pp.1355-1360
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• 2010

In order to search new inhibitors against farnesyl protein transferase (FPTase), a series of 2,3-bis-benzylidenesuccinaldehyde derivatives (1-29) were synthesized and their inhibition activities ($pI_{50}$) against FPTase were measured. From based on the reported results that the inhibitory activities of dimers 2,3-bis-benzylidenesuccinaldehydes were higher than those of monomers cinnamaldehydes, 3D-QSARs on FPTase inhibitory activities of the dimers (1-29) were studied quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The statistical qualities of the optimized CoMFA model II ($r^2{_{cv.}}$= 0.693 and $r^2{_{ncv.}}$= 0.974) was higher than those of the CoMSIA model II ($r^2{_{cv.}}$ = 0.484 and $r^2{_{ncv.}}$ = 0.928). The dependence of CoMFA models on chance correlations was evaluated with progressive scrambling analyses. And the inhibitory activity exhibited a strong correlation with steric factors of the substrate molecules. Therefore, from the results of graphical analyses on the contour maps and of predicted higher inhibitory active compounds, it is suggested that the structural distinctions and descriptors that contribute to inhibitory activities ($pI_{50}$) against FPTase will be able to applied new inhibitor design.

• Applied Biological Chemistry
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• 제41권1호
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• pp.99-103
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• 1998

Triazolopyrimidine sulfonanilide (TP) 유도체는 널리 사용되고 있는 제초제 중의 하나이다. 우리는 TP 유도체 화합물의 골격을 이루고 있는 벤젠 고리를 pyrimidine 고리로 치환시킨 새로운 3 종류의 sulfonamide 유도체(TPP)를 합성하고, 보리에서 추출한 acetolactate synthase (ALS)의 저해 활성도를 측정한 결과 0.005 부터 2 mM 사이의$I_{50}$값을 얻었다. $I_{50}$ 값의 비교에서 pyrimidine 고리에 methyl기가 치환된 TPP 유도체는 methoxy기가 치환된 유도체 보다 높은 저해 활성도를 나타내었다. 또한 triazolopyrimidine 고리에 cyclopentano 고리로 치환된 TPP 유도체는 methyl- 및 phenyl가 치환된 유도체보다 우수한 저해 활성도를 보였다. 따라서 새로운 TPP 유도체의 제초 효력은 치환기에 의한 분자내 전자 분포 변화와 밀접한 관계가 있으나 치환기의 크기에 따른 입체적 장애 요인은 저해 활성도에 전혀 영향이 없음을 알 수 있었다.

• 농약과학회지
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• 제8권3호
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• pp.151-161
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• 2004

새로운 1-(5-methyl-3-phenylisoxazolin-5-yl)methoxy-2-chloro-4-fluorobenzene 유도체들의 phenyl 고리에 R-치환기와 치환기가 도입된 A=3,4,5,6-tetrahyophthalimino, B=3-chloro-4,5,6,7-tetrahydro-2H-indazolyl 및 C=3,4-dimethylmaleimino 치환체들에 의한 벼(Orysa sativa L.)와 논피 (Echinochloa crus-galli) 뿌리와 줄기 부위의 살초활성에 관한 3차원 구조-활성관계(3D-QSAR)를 Gasteiger-Huckel 전하를 사용하여 비교 분자장 분석(CoMFA) 방법으로 연구하였다. 두 초종의 뿌리와 줄기의 살초 활성에 대한 4개의 CoMFA 모델들은 46개 화합물로 구성된 training set로부터 유도되었으며 각 모델들은 8개 화합물의 각 test set에 의하여 예측성이 평가되었다. Standard field, indicator field 및 H-bond field를 조합한 조건(SIH)에서 유도된 모델들의 통계결과는 cross-validated $r^2_{cv.}$값$(q^2=0.635\sim0.924)$과 non cross-validated, $r^2_{ncv}$ $(0.928\sim0.977)$값 그리고 PRESS 값$(0.091\sim0.156)$에 근거하여 매우 양호한 예측성을 나타내었다. 그리고 살초 활성은 분자의 입체장$(74.3\sim87.4%)$, 정전기장$(10.10\sim18.5%)$ 및 소수성장$(1.10\sim8.30%)$과 높은 상관성을 보였으며 입체장이 살초 활성에 가장 중요한 요소이었다. 이같은 CoMFA 분석 결과로부터, 이종 간 선택적이며 고 활성의 protox 저해제들이 X-치환기의 수식에 의하여 설계될 수 있을 것임을 알았다.

• Journal of Microbiology and Biotechnology
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• 제6권3호
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• pp.173-178
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• 1996

Synergic effects among endo-xylanase, $\beta$-xylosidase, and acetyl xylan esterase of Bacillus stearothermophilus in the hydrolysis of xylan were studied by using birchwood, oat spelt, and acetylated xylan as substrates. Synergism between endo-xylanase and $\beta$-xylosidase was observed on all three substrates tested, indicating that $\beta$-xylosidase enhanced the production of xylose by relieving the end-product inhibition upon endo-xylanase conferred by xylooligomers. Endo-xylanase and $\beta$-xylosidase also showed synergism with acetyl xylan esterase in the hydrolysis of birchwood and acetylated xylan, while no synergic effect was detected in oat spelt xylan hydrolysis. Thus, the hydrolysis of xylan containing acetic acid side chains required the action of acetyl xylan esterase, which eliminated the steric hindrance of the side chains, leading to the better hydrolysis by endo-xylanase and $\beta$-xylosidase , and the acetyl xylan esterase activity was also enhanced by endo-xylanase and $\beta$-xylosidase for the latter enzymes provided acetyl xylan esterase with shorter xylan oligomers, the better substrate for the enzyme.

• Applied Biological Chemistry
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• 제33권3호
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• pp.231-238
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• 1990

14종의 새로 합성된 1-(phenxymethyl)benzotriazole(I)(Y=0)과 1-(thiophenoxymethyl)benzotriazole (II)(Y=S) 및 1-(azidomethy) benzotriazole(III) 유도체의 구조와 in vitro에서 Pyricularia oryzae, Fusarium axysporum f.sp.sesami, Valsa ceratosperma 및 Botrytis cinerea에 대한 균사 생장을 50% 저해하는 활성($pI_{50}$)사이의 구조-항균활성 상관관계들을 QSAR방법으로 연구하였다. (I)의 항균활성은 (II)와 (III)보다 우세하였으며 phenoxy group(I)의 치환기 효과는 수소 결합성 (HB)과 포물선 관계의 electronic effect($\sigma$), steric effect($B_1$)그리고 hydrophobic effect($\pi$)로 설명된다. P. oryzae와 F. axysporum f.sp.sesami의 항균 활성에 대한 치환기의 적정값은 $B_1$=1.40A, (H)와 $\sigma=0.07{\sim}0.15$, (H)이고 V. ceratosperma와 B. cinerea에 대하여는 각 각 $\sigma=0.23{\sim}0.28$, (C1)과 $\pi=0.70$, (C1)이었으며 가장 호과적인 화합물인 ( I a)와 ( I d)의 구조-활성관계가 검토되었다.