• Molecules and Cells
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• 제27권6호
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• pp.667-671
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• 2009

Visfatin (Nampt/PBEF) plays a pivotal role in the salvage pathway for $NAD^+$ biosynthesis. Its potent inhibitor, FK866, causes cellular $NAD^+$ levels to decline, thereby inducing apoptosis in tumor cells. In an effort to improve the solubility and binding interactions of FK866, we designed and synthesized IS001, in which a ribose group is attached to the FK866 pyridyl ring. Here, we report the crystal structure of rat visfatin in complex with IS001. Like FK866, IS001 is positioned at the dimer interface, and all of the residues that interact with IS001 are involved in hydrophobic or ${\pi}-{\pi}$-stacking interactions. However, we were unable to detect any strong interactions between the added ribose ring of IS001 and visfatin, which implies that a bulkier modifying group is necessary for a tight interaction. This study provides additional structure-based information needed to optimize the design of visfatin inhibitors.

• Bulletin of the Korean Chemical Society
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• 제35권1호
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• pp.250-252
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• 2014

Lipoprotein-associated phospholipase A2 (Lp-$PLA_2$) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-$PLA_2$ inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-$PLA_2$ through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-$PLA_2$. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

• 대한화학회지
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• 제65권2호
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• pp.106-112
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• 2021

12 kinds of (-)-catechin derivatives were designed and synthesized. The catechin derivatives were evaluated their antioxidant activities using DPPH method. Most of them showed good antioxidant activity, particularly compounds 1d, 1e and 1j exhibited more activity than butylated hydroxytoluene (BHT). Molecular docking studies for compounds 1d, 1e and 1j with STAT1 showed not only sufficent characteristics binding cavity but also agreement with the observed biological activity. Acording to docking results, the compounds showed greater than hydrogen bonding, hydrophobic interactions, electrostatic interactions, and Van der Waals interactions as compared to the reference compound. They formed hydrogen bonds with important residues such as Lys566, His568, Leu570, and Phe644. The compounds showed a novel hydrogen bonding interaction with Arg649, which was not reported previously. Our results might suggest the compounds could serve as a novel anti-oxidant agent.

• 한국수산과학회지
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• 제26권2호
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• pp.133-140
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• 1993

어육연제품의 제조시 가열에 의한 gel화 및 물성을 연구하기 위하여 소수성잔기의 노출 및 SH기의 증감 등 단백질의 성상변화를 측정하였다. 표면소수성 잔기는 $5{\sim}65^{\circ}C$의 범위에서는 온도의 상승에 따라 증가하였으며, $25{\sim}35^{\circ}C$의 온도범위에서 가장 급속히 증가하여 $35^{\circ}C$에는 처음의 약 2배로 증가하였다. 총SH기는 온도의 상승에 따라 감소하여 $85^{\circ}C$에는 처음의 약 $80\%$로 되었으며, $45^{\circ}C$부터 감소속도가 크게 나타난 바니면, 유리 SH기는 $45^{\circ}C$ 이상의 가열에 의해 크게 증가하였다. 이상의 결과들로 미루어 보아 소수성결합은 setting온도에 해당되는 $35^{\circ}C$ 전후에서 주로 형성되며, disulfide결합은 그보다 높은 $45^{\circ}C$ 이상에서 주로 형성됨을 알 수 있었다. 따라서 2단가열을 행함으로써 탄력이 증가되는 원인은 setting과정에서의 소수성결합에 의한 균일한 망상구조의 형성과 본 가열에 의한 disulfide결합의 형성에 기인하는 것으로 추정된다.

• Bulletin of the Korean Chemical Society
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• 제25권9호
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• pp.1331-1335
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• 2004

Angiogenesis is essential for the growth and persistence of solid tumors. Their metastases, anti-angiogenesis could lead to the suppression of tumor growth. One of the main strategies of cancer treatment is developing molecules of anti-angiogenic activity. In this study, two angiogenic inhibitors, Ang3 (KLFDF) and Ang4 (XLFDF) derived from KLYDY, which is the sequence of angiostatin active sites kringle 5, were designed and synthesized. Previously we reported the activities and structures of two inhibitors, Ang1 (KLYDY) and Ang2 (KLWDF). In order to investigate the effect of Phe substitution, Ang3 was designed with a sequence of KLFDF. In order to reduce conformational flexibility of side chain in Lys, Ang4 was designed with a sequence of XLFDF, where X has amino substituted phenyl ring. Solution structures of those inhibitors were investigated using NMR spectroscopy and their activities as angiogenesis inhibitors were studied. Ang1 and Ang2 show angiogenic activities, while Ang3 and Ang4 have no activities and have extended structures compared to Ang1 and Ang2. Therefore, Phe rings do not have effective hydrophobic interactions with other aromatic residues in Ang3 and Ang4. The representative structure of Ang2 has a stable intramolecular hydrogen bond. Therefore, intramolecular hydrogen bonding might be more important in stabilizing the structure than the hydrophobic interactions in these inhibitors. More rigid structure, which can be expected to have higher activities and better match with the receptor bound conformations, can be obtained with a constrained cyclic structure. Further peptidomimetic approaches should be tried to develop angiogenesis inhibitors.

• Journal of Microbiology and Biotechnology
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• 제28권5호
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• pp.671-678
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• 2018

Papiliocin, isolated from the swallowtail butterfly (Papilio xuthus), is an antimicrobial peptide with high selectivity against gram-negative bacteria. We previously showed that the N-terminal helix of papiliocin (PapN) plays a key role in the antibacterial and anti-inflammatory activity of papiliocin. In this study, we measured the selectivity of PapN against multidrug-resistant gram-negative bacteria, as well as its anti-inflammatory activity. Interactions between Trp2 of PapN and lipopolysaccharide (LPS), which is a major component of the outer membrane of gram-negative bacteria, were studied using the Trp fluorescence blue shift and quenching in LPS micelles. Furthermore, using circular dichroism, we investigated the interactions between PapN and LPS, showing that LPS plays critical roles in peptide folding. Our results demonstrated that Trp2 in PapN was buried deep in the negatively charged LPS, and Trp2 induced the ${\alpha}$-helical structure of PapN. Importantly, docking studies determined that predominant electrostatic interactions of positively charged arginine residues in PapN with phosphate head groups of LPS were key factors for binding. Similarly, hydrophobic interactions by aromatic residues of PapN with fatty acid chains in LPS were also significant for binding. These results may facilitate the development of peptide antibiotics with anti-inflammatory activity.

• 한국응용과학기술학회지
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• 제37권2호
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• pp.250-259
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• 2020

가용화현상에 있어서 유기물(피가용화물)과 계면활성제와의 상호관계를 조사하고자 UV-Vis 법을 이용하여 가용화상수(K_s)값을 구하였다. 유기물의 para-위치에 알킬치환기가 도입된 4-alkylanilines과 양이온계면활제인 소수기 길이가 서로 다른 DTAB, TTAB, CTAB를 이용하여 유기물과 계면활성제간의 소수성 상호작용에 따른 가용화 상수값과 그에 따른 열역학함수들을 다양한 온도에서 구하여 서로 비교하였다. 그 결과 유기물에서 알킬치환기에 의한 소수성효과는 탄소사슬의 길이가 증가할수록 일정한 비율로 증가하였고, 또한 계면활성제에서 소수기의 길이효과도 일정한 비율로 증가하였다. 그런데 이러한 소수성 효과는 유기물에서 알킬치환기에 의한 효과가 계면활성제에서 소수기의 효과 보다 더 크게 나타났다. 또한 계산된 열역학 함수값들의 결과들로부터 유기물의 소수성이 증가할수록 그리고 계면활성제의 소수성이 증가할수록 유기물은 미셀내부의 더 깊은 곳으로 가용화됨을 알 수 있었다. 등구조온도는 실험 조건 범위 내에서 큰 차이를 보이지 않았으며, 최대값과 최소값의 차이가 1K미만으로 차이가 거의 없는 것으로 나타났다.

• 한국지하수토양환경학회:학술대회논문집
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• 한국지하수토양환경학회 2000년도 추계학술대회
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• pp.171-176
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• 2000

Bioremediation of hazardous hydrophobic organic compounds, such as polycyclic aromatic hydrocarbons (PAHs), is a major environmental concern due to their toxic and carcinogenic properties. Due to their hydrophobicity, the hydrophobic organic compounds are mainly associated with the soil organic matter or nonaqueous-phase liquids. A major question concerns the relationships between biodegradation and sorption. This work develops and utilizes a non- steady state model for evaluating the interactions between sorption and biodegradation of phenanthrene, a 3-ring PAH compound, in soil-slurry systems. The model includes sorption/desorption of a target compound, its utilization by microorganisms as a primary substrate existing in the dissolved phase and/or the sorbed phase in biomass and soil, oxygen transfer, and oxygen utilization as an electron acceptor. Biodegradation tests with phenanthrene were conducted in liquid and soil-slurry systems. The soil-slurry tests were performed with very different mass transfer rate: fast mass transfer in a flask test at 150 rpm, and slow mass transfer in a roller-bottle test at 2 rpm. In the slurry tests, phenanthrene was degraded more rapidly than in liquid tests, but with a similar rate in both slurry systems. Modeling analyses with several hypotheses indicate that a model without biodegradation of compound sorbed to the soil was not able to account for the rapid degradation of phenanthrene, particularly in the roller bottle slurry test. Reduced mass-transfer resistance to bacteria attached to the soil is the most likely phenomenon accounting for rapid sorbed-phase biodegradation.

• Bulletin of the Korean Chemical Society
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• 제31권12호
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• pp.3740-3744
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• 2010

A typically designed 'Peptide Lego' has two distinct surfaces: a hydrophilic side that contains the complete charge distribution and a hydrophobic side. In this article, we describe the fabrication of a unique lego-type peptide with the AEAEYAKAK sequence. The novel peptide with double amphiphilic surfaces is different from typical peptides due to special arrangement of the residues. The results of CD, FT-IR, AFM and DLS demonstrate that the peptide with the random coil characteristic was able to form stable nanostructures that were mediated by non-covalent interactions in an aqueous solution. The data further indicated that despite its different structure, the peptide was able to undergo self-assembly similar to a typical peptide. In addition, the use of hydrophobic pyrene as a model allowed the peptide to provide a new type of potential nanomaterial for drug delivery. These efforts collectively open up a new direction in the fabrication of nanomaterials that are more perfect and versatile.

• Bulletin of the Korean Chemical Society
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• 제6권3호
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• pp.145-148
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• 1985

The effect of anionic polyelectrolytes, poly(styrenesulfonate) (PSS) and poly(vinylsulfonate) (PVS), on the charge transfer complexing between indole derivatives and methyl viologen($MV^{++}$) cation was investigated. The results were compared with effect of NaCl and an anionic surfactant, sodium dodecylsulfate (SDS). Both PSS and PVS enhanced the complex formation of neutral species (indole and indole acetate at low pH), zwitter ionic tryptophan, and positively charged tryptamine and tryptophan at low pH with $MV^{++}$. This result was attributed to the contribution of hydrophobic interaction, in addition to electrostatic interaction. The enhancing effect of PSS was much higher than that of PVS reflecting the higher hydrophobicity of PSS. The interaction between indole acetate anion and $MV^{++}$ was greatly reduced by addition of PVS and PSS. The higher charge density of PVS was appeared as greater reducing effect indicating the importance of electrostatic force in this case. In all cases, the effect of polyelectrolytes showed maxima, and further addition of PVS and PSS decreased the effect. This behavior was explained in terms of distribution of indole derivatives and $MV^{++}$ in domain of polyanions. The complex formation constants and molar absorptivities of complexes were determined, and the values were compared with those in water and SDS solutions.