• 생명과학회지
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• 제33권11호
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• pp.868-875
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• 2023

Kinesin-1은 kinesin superfamily (KIF) 단백질 중에서 처음으로 확인된 모터 단백질로 세포내 미세소관 의존하여 세포내 cargo를 수송한다. Kinesin-1은 두 개의 중쇄(KHC, 또는 KIF5)와 두 개의 경쇄(KLC)로 구성된다. KIF5A의 C-말단의 93개 아미노산은 KIF5B와 KIF5C의C-말단 꼬리 영역과는 상동성이 없다. 본 연구에서 우리는 KIF5A의 C-말단 영역과 특이적으로 결합하는 단백질을 분리하기 위해 효모 2-하이브리드 스크리닝을 하였다. 본 연구에서 우리는 KIF5A와 결합하는 단백질로 유비퀴틴화 경로 및 단백질 수송에 관여하는 어댑터 단백질로 기능하는 CUE 도메인을 가진 CUEDC2를 확인하였다. CUEDC2는 KIF5A의 C-말단 영역과 결합하지만, KIF5B, KIF3A 및KLC1과는 결합하지 않았다. KIF5A는 CUEDC2의 C-말단 영역과 특이적으로 결합하였지만, CUEDC2의 다른 isoform인 CUEDC1과는 결합하지 않았다. 또한, KIF5A와 CUEDC2의 결합은 글루타티온 S-트랜스퍼라제(GST) 풀다운으로 단백질간 결합을 확인하였다. HEK-293T 세포에서 myc-KIF5A와 FLAG-CUEDC2을 공동 발현되었을 때, CUEDC2는 kinesin-1과 공동 면역 침전되었고, myc-KIF5A와 EGFP-CUEDC2는 세포내의 같은 위치에서 발현하였다. 이러한 결과들은 kinesin-1에 의한 세포내 화물 수송에서 CUEDC2는 KIF5A에 결합하여 kinesin-1과 화물을 연결하는 어댑터 단백질 역할을 시사한다.

• 생물정신의학
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• 제1권1호
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• pp.67-78
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• 1994

The author examined the relationship of two markers, D5S39(p105-153Ra), D5S76(p105-599Ha) of chromosome 5 and $D_2$, $D_3$ receptor genes in a Korean schizophrenic pedigree using polymerase chain reaction(PCR). The results were as follows : 1) On D5S39 locus, 5 different alleles(224/226 bp : 4 cases, 218/226 bp : 3 cases, 222/226 bp : 3 cases, 218/230 bp : 1 case, 222/224 bp : 1 case) were produced. 2) On D5S76 locus, 5 different alleles(102/112 bp : 4 cases, 94/112 bp : 3 cases, 108/112 bp 3 cases, 94/94 bp : 1 case, 102/108 bp 1 case) were produced. 3) On $D_2$ receptor gene, 3 different alleles($A_1A_2$ : 8 cases, $A_1A_1$ : 2 cases, $A_2A_2$ : cases) were produced. 4) On $D_3$ receptor gene, 2 different alleles(1/2 : 7 cases, 1/1 : 5 cases) were produced. The author had not find any specific alleles on all four loci in all pedigree nor any specific alleles in the schizophrenic patients. Though the author has not found absolute relationship between the four loci and the onset of schizophrenia, there still remains the possibilities if the more detailed and elaborated pedigree studies are done.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3305-3311
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• 2012

Background: The present study aimed to find the prognostic implications of two polymorphisms in TP53 (p.R72P, PIN3 Ins16bp) and one in CCR5 ($CCR5{\Delta}32$) in sporadic breast cancer patients. Methods: DNA samples of 80 breast cancer patients and 80 age and gender matched unrelated healthy control individuals from Punjab, North West India were analyzed. Results: For p.R72P, the genotype frequency was 13.8% (RR), 58.8% (RP), 27.5% (PP) in patients and 33.9% (RR), 40.0% (RP), 26.5% (PP) in controls. For PIN3 Ins16bp, the genotype frequencies were 53.75% (A1A1), 37.5% (A1A2), 8.75% (A2A2) in patients and 66.3% (A1A1), 31.3% (A1A2), 2.5% (A2A2) in controls. Only 4 (5%) breast cancer patients were heterozygous for $CCR5{\Delta}32$ deletion. Common RR-A1A1-WT/WT genotype was lower while RP-A1A2-WT/WT genotype was higher in patients as compared to controls. RP-A1A1-WT/WT genotype was significantly higher in patients as compared to control individuals (p = 0.008). Conclusion: Though a clear association of any particular genotype with sporadic breast cancer or stage was not apparent, the results of present study were suggestive that sporadic breast cancer patients with RR-A1A1-WT/WT genotype might have a better response to chemotherapy, thus improving their chances of survival.

• 약학회지
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• 제52권6호
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• pp.488-493
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• 2008

2-Aminothiazole ring as a bioisoster of catechol in dopamine has provided with good oral availability and lipophilic property. 2-Aminoindan, is a rigid form of dopamine, was evaluated as a dopamine D3 agonist with low neurotoxicity. Dopamine D3 agonist was evaluated as selective for the treatment of Parkinson's disease. In order to develop a novel dopamine D3 agonist, we tried to synthesize the aminothiazoloindenoxazine derivative that is a hybrid structure of aminoindenoxazine and thiazole ring. cis-2-Amino-1-indanol (2) was synthesized from 1,2-indandione-2-oxime by catalytic hydrogenation and it was treated with chloroacetyl chloride and NaH in benzene solution to give (${\pm}$)-cis-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one (6). Nitration of 6 by the mixed acid gave 8-nitro compound (7) and the carbonyl group of 7 was reduced with $LiAlH_4$ to afford compound (8). 8 was reduced to form (${\pm}$)-cis-8-amino-2,3,4,4a,5,9b-hexahydroindeno[1,2-b][1,4]oxazine (9) and finally it was cyclized with KSCN in glacial acetic acid to yield (${\pm}$)-cis-8-amino-2,3,4,4a,5,10b-hexahydrothiazolo[4,5-f]indeno[1,2-b][1,4]oxazine (10).

• 약학회지
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• 제48권2호
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• pp.135-140
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• 2004

For the development of new COX-2 inhibitors, 1,5-diarylhydantoins 5a∼5c and 1,5-diaryl-2-thiohydantoin 6a∼6c were synthesized from commercially available phenylacetic acids through esterification, bromination, C-N bond formation and cyclization. Esters 2a∼c were efficiently synthesized from the starting materials 1a∼c by refluxing in absolute methanol for 3 hours with catalytic concentrated sulfuric acid. Bromination of 2a∼c was carried out with use of N-bomosuccinimide at rt in dichloromethane. The bromine of 3a∼c was substituted with aniline in ethanol or N,N-dimethylformamide to provide 4a∼c. Hydantoins and 2-thiohydantoins were synthesized from 4a∼c by treatment of potassium isocyanate or potassium thiocyanate in dil-ethanol with triethylamine.

• 전자공학회논문지
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• 제52권12호
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• pp.134-141
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• 2015

본 연구의 목적은 1.0 mol 고농도 가돌리늄 조영제가 기존의 0.5 mol MR 조영제에 비해 얼마나 높은 신호강도를 보이는지를 정량적으로 비교 분석하는 것이다. 실험을 위하여 1.0 mol Gadobutrol과 0.5 mol Gadoteridol을 사용하여 희석비율을 달리한 각각의 MR팬텀을 제작하였다. 이를 1.5T MR장비의 조영증강 T1 검사인 2D SE 와 Head-Neck Angio의 3D FLASH 두 가지 방법으로 스캔하였다. 이후 영상에서 희석비율별 신호 강도를 측정하여 이를 비교 분석하였다. 두 개의 시퀀스(2D SE, 3D FLASH)에서의 조영증강 반응시작 지점인 RSP(Reaction Starting Point)는 0.5 mol에서는 두 시퀀스 각각 6.0%, 60.0%, 1.0mol에서는 2.0%, 20.0%로 0.5 mol 조영제서의 조영증강반응이 빨리 일어났다. 최대 신호강도인 MPSI(Max Peak Signal Intensity)는 0.5 mol에서 두 시퀀스 각각 1358.8[a.u], 1573.0[a.u], 1.0mol 에서는 1374.9[a.u], 1642.4[a.u]로 최대신호강도는 두 조영제 모두 비슷하였다. 더불어 최대신호강도를 보이는 희석비율 지점인 MPP(Max Peak Point)는 0.5 mol 에서는 두 시퀀스에서 각각 0.4%, 10.0%, 1.0mol 에서는 0.16%, 1,8%로 0.5 mol 조영제의 최대신호강도가 더 빨리 형성되었다. 각 희석비율에서의 조영증강 반응면적 RA(Reaction Area)는 0.5 mol 에서는 두 시퀀스 각각 20747.4[a.u], 23204.6[a.u], 1.0 mol 에서는 12691.9[a.u], 20747.4[a.u]로 0.5 mol 조영제가 두 시퀀스에서 각각 27.4%, 11.8% 더 높았다. 본 연구를 통하여 조영증강 T1과 Head-Neck Angio 검사에서 1.0 mol 고농도 가돌리늄 조영제가 0.5 mol MR조영제에 비하여 신호반응이 느리다는 사실을 확인하였으며, 최대 신호강도인 MPSI는 1.0 mol 조영제와 0.5 mol 조영제 둘 다 비슷하여 1.0 mol 고농도 가돌리늄 조영제가 MR영상에서 반드시 높은 신호강도를 보여주지 않는다는 것을 확인 할 수 있었다.

• Bulletin of the Korean Chemical Society
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• 제25권12호
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• pp.1769-1774
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• 2004

Jun/Fos, a crucial factor in transmitting the tumor-promoting signal from the extracellular environment to the nuclear transcription machinery, has a dimerization interface possessing several coiled structural properties. Jun and Fos can interact with the DNA regulatory region, AP-1 (Activator Protein-1), which is composed of 5'-TGAC/GTCA-3'.$^1$ Curcumin is a well-known anticancer and anti-inflammatory compound.$^{2,3}$ It also acts as an inhibitor of the Jun-Fos function. c-Fos and c-Jun with a bZIP region are overexpressed in BL21 E. coli and purified with an $Ni^{2+}$ affinity column. The inhibitors of Fos-Jun-AP-1 complex formation were searched through the EMSA (electrophoresis mobility shift assay) experiment, and new curcuminoids were synthesized and investigated as to their inhibitory effect on the same system. Two curcuminoids showed a stronger inhibitory effect than curcumin. This inhibitory activity was quantified with EMSA. 1,7-bis(4-methyl)-1,6-heptadiene-3,5-dione (BJC003) and 1,7-bis(4-hydroxy-5-methoxy-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC005) showed remarkably high inhibitory activities. $IC_{50}$ of 1,7-bis(4-methyl)-1,6-heptadiene-3,5-dione (BJC003) and 1,7-bis(4-hydroxy-5-methoxy-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC005) are 8.98 ${\mu}M$ and 5.40 ${\mu}M$, respectively. However, 1,7-bis(4-methyl-3-nitrophenyl)-1,6-heptadiene-3,5-dione (BJC004) did not show inhibitory activity.

• Molecules and Cells
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• 제20권1호
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• pp.43-50
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• 2005

Glutaredoxin (Grx) is a small, heat-stable redox protein acting as a multi-functional glutathione (GSH)-dependent disulfide oxidoreductase. We have cloned the monothiol Grx5 gene from the genomic DNA of the fission yeast Schizosaccharomyces pombe. It has 1,904 bp, with one intron, and encodes a putative protein of 146 amino acids with a molecular mass of 16.5 kDa. Recombinant Grx5 produced functional Grx in S. pombe cells. NO-generating sodium nitroprusside (SNP, 1.0 and 2.0 mM) and potassium chloride (KCl, 0.2 and 0.5 M) increased the synthesis of ${\beta}$-galactosidase from a Grx5-lacZ fusion gene, and transcription of Grx5 was also enhanced by SNP and KCl. Synthesis of ${\beta}$-galactosidase from the Grx5-lacZ fusion was lower in Pap1-negative TP108-3C cells than in wild type KP1 cells, and when Pap1 was overproduced in KP1 cells, the level of ${\beta}$-galactosidase increased. We also found that Pap1 is involved in the induction of Grx5 by SNP and KCl. S. pombe Grx5 may play a crucial role in responses to nitrosative and osmotic stresses.

• Bulletin of the Korean Chemical Society
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• 제14권2호
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• pp.287-291
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• 1993

Catalytic iminohydroacylation has been achieved by the reaction of aldimine 1 and 1,5-hexadiene (2a) with Wilkinson's complex as catalyst. Compounds 7a, 8a and 9a were obtained as final product after hydrolysis of the resulting iminohydroacylation products 4a, 5a and 6a. Depending on the reactant ratio (2/1), the ratio of products were changed dramatically : As the 2/1 ratio was increased, 7a is the major product after hydrolysis while 8a is the major with an 1/1 ratio of 2/1. The mechanism of the formation of 5a is determined by the reaction of 1 and 2b under the identical reaction conditions. Considering that 5a may not be formed from the hydroiminoacylation of 14a since 5b cannot be formed from that of conjugate diene 14b generated from isomerization of 2b, 5a must be formed from the reaction of 4a and 10 by addition-elimination mechanism.

• 약학회지
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• 제50권6호
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• pp.403-408
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• 2006

1-Amino-5,6-dimethoxyindan hydrochloride was synthesized from 3- (3,4-dirnethoxyphenyl)propionic acid by intramolecular Friedel-Crafts acylation, oximation with hydroxylamine, and reduction with an overall yield of 74%. 2-Amino-5,6-dimethoxyindan hydrochloride was synthesized from 3-(3,4-dirnethoxyphenyl)propionic acid by intramolecular Friedel-Crafts acylation, oximation with isoamylnitrite, reduction in NaOH and reaction with HCI to form 5,6-dimethoxy-2-indanone, which was reacted with hydroxylamine and reduced with an overall yield of 42%. 5,6-Dimethoxyindan-1,2-dione-2-oxime, which was catalytically hydrogenated to afford cis-, and trans-1-amino-5,6-dimethoxyindan-1-ol as 3 : 1 ratio. This mixture was treated with Li and reacted with chloroacetyl chloride. Cis isomer was acylated and cyclized to synthesize rir -( ${\pm}$ )-7,8-dimethoxy-4,4a,5,9b-tetrahydroindeno[1,2-b][1,4]oxazin-3(2H)-one, but trans isomer was just acylated to form amide.