• Bulletin of the Korean Chemical Society
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• 제31권4호
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• pp.874-880
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• 2010

A series of 13- and 14-membered cyclic enkephalin analogs based on the moderately $\mu$ selective prototype compound Tyr-C[D-$A_2bu$-Gly-Phe-Leu] 8a were synthesized to investigate the structure-activity relationship. The modifications of sequence were mainly focused on two positions 3 and 5, critical for the selective recognition for $\mu$ and $\delta$ opioid receptors. The substitution of hydrophobic $Leu^5$ with hydrophilic $Asp^5$ derivatives led to Tyr-C[D-$A_2bu$-Gly-Phe-Asp(N-Me)] 7 and Tyr-C[D-Glu-Phe-gPhe-rAsp(O-Me)] 5, the peptides with a large affinity losses at both $\mu$ and $\delta$ receptors. The substitution of $Phe^3$ with $Gly^3$ led to Tyr-C[D-Glu-Gly-gPhe-rLeu] 3 and Tyr-C[D-Glu-Gly-gPhe-D-rLeu] 4, the peptides with large affinity losses at $\mu$ receptors, indicating the critical role of phenyl ring of $Phe^3$ for $\mu$ receptor affinities. One atom reduction of the ring size from 14-membered analogs Tyr-C[D-Glu-Phe-gPhe-(L and D)-rLeu] 6a, 6b to 13-membered analogs Tyr-C[D-Asp-Phe-gPhe-(L and D)-rLeu] 1, 2 reduced the affinity at both $\mu$ and $\delta$ receptors, but increased the potency in the nociceptive assay, indicating the ring constrain is attributed to high nociceptive potency of the analogs. For the influence of D- or L-chirality of $Leu^5$ on the receptor selectivity, regardless of chirality and ring size, all cyclic diastereomers displayed marked $\mu$ selectivity with low potencies at the $\delta$ receptor. The retro-inverso analogs display similar or more active at $\mu$ receptor, but less active at $\delta$ receptor than the parent analogs.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.209-214
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• 2009

The striatum receives glutamatergic afferents from the cortex and thalamus, and these synaptic transmissions are mediated by ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl D-aspartate (NMDA) receptors. The purpose of this study was to characterize glutamate receptors by analyzing NMDA/AMPA ratio and rectification of AMPA and NMDA excitatory postsynaptic currents (EPSCs) using a whole-cell voltage-clamp method in the dorsal striatum. Receptor antagonists were used to isolate receptor or subunit specific EPSC, such as (DL)-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, ifenprodil, an NR2B antagonist, CNQX, an AMPA receptor antagonist and IEM-1460, a GluR2-lacking AMPA receptor blocker. AMPA and NMDA EPSCs were recorded at - 70 and + 40 mV, respectively. Rectification index was calculated by current ratio of EPSCs between + 50 and - 50 mV. NMDA/AMPA ratio was 0.20${\pm}$0.05, AMPA receptor ratio of GluR2-lacking/GluR2-containing subunit was 0.26${\pm}$0.05 and NMDA receptor ratio of NR2B/NR2A subunit was 0.32${\pm}$0.03. The rectification index (control 2.39${\pm}$0.27) was decreased in the presence of both APV and combination of APV and IEM-1460 (1.02${\pm}$0.11 and 0.93${\pm}$0.09, respectively). These results suggest that the major components of the striatal glutamate receptors are GluR2-containing AMPA receptors and NR2A-containing NMDA receptors. Our results may provide useful information for corticostriatal synaptic transmission and plasticity studies.

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.261-269
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• 2012

The cyclic dimers of enkephalin were isolated as minor components during the solution synthesis of the corresponding cyclic monomers. The ratio of cyclic dimer to monomer was approximately 1:4 from the percent of yields. In the receptor binding assay of two cyclic dimmers, ($Tyr_2-C[D-Glu-Phe-gPhe]_2$ 6, $Tyr_2-C[D-Asp-Phe-gPhe-rLeu]_2$ 8), both analogs exhibited the high preference for ${\delta}$ receptor compared to monocyclic counterparts. In the nociceptive activity, both showed about 5 times less potent than the cyclic monomers. The repeated synthesis of 14-membered cyclic analog, Tyr-C[D-Glu-Phe-gPhe-D-rLeu] 14, which was known as having three distinct cis-trans isomers, gave rise to apparently different conformational analog arousing only trans isomer. In the receptor binding assay, it showed tremendously high selectivity toward ${\mu}$ receptor $({\delta}/{\mu}=160)$.

• The Korean Journal of Physiology and Pharmacology
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• 제11권4호
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• pp.139-144
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• 2007

Recent studies suggest that alterations in glutamate receptor subunit levels in mesocorticolimbic dopamine areas could account for neural adaptations in response to psychostimulant drugs. Although many drugs of abuse induce changes in ionotropic glutamate receptor subunits in mesocorticolimbic dopamine areas, the changes of ionotropic glutamate receptor subunits by repeated nicotine treatment in these areas are not known. To answer this question, we injected male Sprague-Dawley rats twice daily with nicotine (0.4 mg/kg) or saline (1 ml/kg) for 10 days. The immunoreactivity of NR1, GluR1, and GluR2 glutamate receptor subunits was examined $16{\sim}18 h$ after the last injection of saline or nicotine. Repeated nicotine treatment significantly increased NR1 levels in the ventral tegmental area (VTA). In addition, repeated nicotine treatment showed a tendency towards an increase in GluR1 levels in the VTA as well as in striatum. However, there was no significant change in glutamate receptor subunits in other areas including nucleus accumbens (NAc). These results demonstrate that repeated nicotine treatment increases NR1 levels in VTA similarly to other drugs of abuse, suggesting that elevated glutamate receptor subunits in the VTA, but not NAc may be involved in the excitation of mesocorticolimbic dopamine neurons by nicotine.

• 대한약리학회:학술대회논문집
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• 대한약리학회 2006년도 The 6th Congress of the Federation of Asian and Oceanian Physiological Societies
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• pp.82.2-82.2
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• 2006

• 한국동물학회:학술대회논문집
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• 한국동물학회 2000년도 한국생물과학협회 학술발표대회
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• pp.222.1-222
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• 2000

No Abstract, See Full Text

• 한국미생물·생명공학회지
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• 제29권4호
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• pp.248-252
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• 2001

메탄올 자화효모 Hansenula polymorpha 가 생산하는 재조합 인체 알부민 (human albumin)을 heat treatment ultrafiltration phenyl Sepharose CL-4B Mono Q 컬럼 크로마토그래피를 수행하여 수율 60%로 정제하였다. 정제된 재보합 알부민 SDS-PAGE를 수행한 결과 분자량이 65,000 Da으로 나타났고, 본 재조합 알부민의 N-말단 아미노산 서열은 Asp- Ala- His- Lys- Ser- Glu- Ala 으로 혈청유래 알부민 및 다른 효모 유래의 재조합 인체 알부민 과 동일함을 보였다. 정제한 재조합 인체 알부민의 아미노산 조성은 총 18종 의 아미노산이 검출되었고 아미노산 잔기 중 cysteine, arginine lysine 등이 이론치와 일치하였으며, 혈청 알부민과 동일하게 약 pI 4.8 정도 값을 나타내어 H. polymorpha 유래의 재조합 단백질의 전반적인 아미노산 구성이 혈청 알부민과 동일함을 확인하였다.

• 한국가금학회지
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• 제35권2호
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• pp.183-190
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• 2008

본 실험은 Beta-glucan 제제들이 산란계의 생산성, 혈액성상, 소장내 미생물 균총 및 면역 체계에 미치는 영향을 측정하기 위해 실시하였다. 사양 실험은 40주령의 산란계(Hy-Line Brown) 720수를 선별하여 A형 2단 케이지에 대조구 포함 총 5처리구로 구성하여 처리당 4반복 반복당 36수씩 randomized block design으로 배치하였다. 시험 기간 동안 물과 사료는 자유 섭취하게 하였으며 일반적인 점등 관리(자연일조+조명:16 hr)를 실시하였다. 시험구는 대조구, $BetaPolo^{(R)}$ (미생물 발효 ${\beta}-glucan$, 수용성)구, $HiGlu^{(R)}$(미생물 발효 ${\beta}-glucan$)구, $OGlu^{(R)}$(Oat ${\beta}-glucan$)구 그리고 $BGlu^{(R)}$(Barley ${\beta}-glucan$)구 등 5처리구로 두었다. 생산성에 있어서 일계 산란율은 처리간에 유의한 차이가 없었으나 hen-housed egg production에 있어서 OGlu구가 HiGlu 구에 비해 유의하게 낮았다. 사료 섭취량과 사료 요구율은 처리간에 유의한 차이가 있었는데 모든 ${\beta}-glucan$처리구들이 대조구에 비해 낮았다. 계란 품질에 있어서 난각 강도는 대조구에 비해 모든 ${\beta}-glucan$ 처리구들이 유의하게 높았고 그 중에서 BGlu구가 가장 높았다. 난각색과 Haugh unit는 ${\beta}-glucan$ 처리구들이 대조구보다 낮았는데 특히 OGlu구가 가장 낮았다. 혈액성상에 있어 leucocytes는 전반적으로 ${\beta}-glucan$ 처리구들이 대조구보다 낮았다. Erythrocytes 중 적혈구 용적율(HCT)과 평균적혈구용적(MCV)은 처리간에 유의한 차이가 있었는데 MCV는 ${\beta}-glucan$ 처리구들이 대조구에 비해 높은 수준을 보였다. 특히 ${\beta}-glucan$ 처리구중에서 OGlu구가 leucocytes와 erythrocytes 수준이 가장 높았다. 소장내 미생물 균총도 처리간 유의적 차이가 없었으나 Cl. perfringens 의 경우 모든 ${\beta}-glucan$ 처리구에서 대조구에 비하여 감소하는 경향을 보였다. 난황내 IgY 함량에 있어서는 전체적으로 유의적인 차이는 없으나 시험 마지막 5기에 ${\beta}-glucan$ 처리구 들에서 증가하는 경향을 보였다. 혈액내 IgG, IgA 함량에 있어서는 유의적 차이가 없었다. 이상의 결과를 종합해보면 산란계에 ${\beta}-glucan$ 제제들의 급여가 사료 요구율과 난각 강도를 유의하게 개선시켰는데 혈액성상, 장내 미생물 균총, 면역 기능 등에 순기능적 개선에 의한 결과라고 사료된다.

• Bulletin of the Korean Chemical Society
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• 제23권4호
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• pp.593-597
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• 2002

(R,S)- and (R)-2-Benzylcysteine (1) and (R,S)-2-phenethylcysteine (2) were synthesized and evaluated as inhibitors for carboxypeptidase A (CPA) with the expectation that these compounds exhibit improved inhibitory activities over 2-benzyl-3-mercaptopropanoic acid (BMPA), a potent CPA competitive inhibitor, possibly having additional interactions of their amino group with the carboxylate of Glu-270 of the enzyme upon binding to CPA. Contrary to the expectation, however, the CPA inhibitory potencies of these compounds were found to be much reduced compared with that of BMPA, suggesting that the amino group in the inhibitors rather exerts steric hindrance in binding of these inhibitors to CPA.

• Journal of Korean Neurosurgical Society
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• 제41권1호
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• pp.30-38
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• 2007

Objective : To elucidate the role of aquaporin-4[AQP4] in cerebral edema formation, we studied the expression and subcellular localization of AQP4 in astrocytes after focal cerebral ischemia. Methods : Cerebral ischemia were induced by permanent middle cerebral artery[MCA] occlusion in rats and estimated by the discoloration after triphenyltetrazolium chloride[TTC] immersion. Change of AQP4 expression were evaluated using western blot. Localization of AQP4 was assessed by confocal microscopy and its interaction with ${\alpha}-syntrophin$ was analyzed by immunoprecipitation. Results : After right MCA occlusion, the size of infarct and number of apoptotic cells increased with time. The ratio of GluR1/GluR2 expression also increased during ischemia. The polarized localization of AQP4 in the endfeet of astrocytes contacting with ventricles, vessels and pia mater was changed into the diffuse distribution in cytoplasm. The interactions of AQP4 and Kir with ${\alpha}-syntrophin$, an adaptor of dystrophin complex, were disrupted by cerebral ischemia. Conclusion : The deranged spatial buffering function of astrocytes due to mislocalized AQP4/Kir4.1 channel as well as increased assembly of $Ca^{2+}$ permeable AMPA receptors might contribute to the development of edema formation and the excitotoxic neuronal cell death during ischemia.