• Bulletin of the Korean Chemical Society
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• 제32권2호
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• pp.620-624
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• 2011

In recent years, the study of self-assembly peptide used in drug delivery system has been attracted great interest from scientists. In the category are self-assembly peptides in the structure either with one hydrophobic surface and another hydrophilic or a hydrophobic head and a hydrophilic tail. Here, we focus on a novel designed peptide EYK with double amphiphilic surfaces, investigating on the capability of peptide as a carrier for hydrophobic compound model pyrene. The fluorescence data presented the dynamic process of the transfer, showing that the pyrene was in the crystalline form in peptide solution, and molecularly migrated from its peptide encapsulations into the membrane bilayers when the peptide-pyrene suspension was mixed with liposome vesicles. The results indicated that the peptide EYK could stabilize hydrophobic pyrene in aqueous solution and delivered it into EPC liposome as a potential carrier.

• Bulletin of the Korean Chemical Society
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• 제35권3호
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• pp.783-792
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• 2014

The binding interaction between a hemolytic peptide ${\delta}$-lysin and a zwitterionic lipid bilayer POPC was investigated through a series of molecular dynamics (MD) simulations. ${\delta}$-Lysin is a 26-residue, amphipathic, ${\alpha}$-helical peptide toxin secreted by Staphylococcus aureus. Unlike typical antimicrobial peptides, ${\delta}$-lysin has no net charge and it is often found in aggregated forms in solution even at low concentration. Our study showed that only the monomer, not dimer, inserts into the bilayer interior. The monomer is preferentially attracted toward the membrane with its hydrophilic side facing the bilayer surface. However, peptide insertion requires the opposite orientation where the hydrophobic side of peptide points toward the membrane interior. Such orientation allows the charged residues, Lys and Asp, to have stable salt bridges with the lipid head-group while the hydrophobic residues are buried deeper in the hydrophobic lipid interior. Our simulations suggest that breaking these salt bridges is the key step for the monomer to be fully inserted into the center of lipid bilayer and, possibly, to translocate across the membrane.

• 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.

• 한국환경과학회지
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• 제12권1호
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• pp.77-80
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• 2003

The interaction of mastoparan B, a cationic tetradecapeptide amide isolated from the hornet Vespa basalis, with phospholipid bilayers was studied with synthetic mastoparan B and its analogue with Ala instead of hydrophobic 12th amino acid residue in mastoparan B. MP-B and its derivative, [12-Ala]MP-B were synthesized by the solid-phase peptide synthesis method. MP-B and its analogue, [12-Ala]MP-B adopted an unordered structure in buffer solution. In the presence of neutral and acidic liposomes, the peptides took an $\alpha$-helical structure. The two peptides interacted with neutral and acidic lipid bilayers. These results indicated that the hydrophobic face in the amphipathic $\alpha$-helix of MP-B critically affected the biological activity and helical content.

• 생명과학회지
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• 제8권1호
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• pp.102-108
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• 1998

Gltcosylphosphatidylinositol (GPI)에 의해 고정된 단백질의 초기 형태는 골지체에서의 직접적인 processing을 수행하기 위한 아미노와 카르 복시 말단의 hydrophobic signal sequence를 소유하고 있다. 앞서, mouse 임파구로부터 NAD;arginine ADP-ribosyltransferase (Yac-1)가 클로닝되었으며 Yac-1 transferase의 아미노산 배열을 추정해 본 결과, hydrophobic 아미노와 카르복시 말단을 포함하고 있었으며 이는 GPI-anchroed 단백질들의 알려진 signal sequence와 일치하였다. 미 transferase는 야생형의 cDNA로 transfection된 NMU (rat mammary adenocarcinoma) cell의 표면에 존재하였으며 phosphoatidylinosotol-specific phospholipase C에 의해 방출되어졌다. 카르복시 말단의 hydrophobic sequence가 없는 돌연변이체는 수용성이며 분비성인 transferase를 생산하였다. 이러한 사실은 카르복시 말단의 sequence가 없는 돌연변이체는 수용성이며 분비성인 transferase를 생산하였다. 이러한 사실은 카르복시 말단의 sequence가 GPI의 부착에 중요함을 나타내준다.

• Archives of Pharmacal Research
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• 제28권7호
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• pp.756-760
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• 2005

Polyene macrolide amphotericin B (AmB) is the drug of choice for the treatment of disseminated fungal infections. However, because of its pronounced side effects, the drug has limited applicability. There are few interesting reports, which state that co-administration of the drug with homo-peptide of polyaspartic acid reduces the side effects of the drug. In our present study, an approach has been made to systematically synthesize low molecular weight heteropeptides consisting of L-aspartic acid and its derivative. It was hypothesized that such heteropeptides will reduce the toxic side effects of the drug by facile hydrophobic binding between the polymer and the drug. We have employed the strategy of solid phase peptide synthesis (SPPS) to synthesize low molecular weight hetero-peptides by using L-aspartic acid and benzyl-L-aspartic acid to induce the hydrophobic binding between the peptide and the drug. In future, the proposed methodology can be employed to tailor other polypeptides substituted with benzyl groups to reduce the nephrotoxicity of AmB.

• 한국자기공명학회논문지
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• 제15권1호
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• pp.1-13
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• 2011

9Pbw2 is a 9-mer analog of protaetiamycine derived from the larvae of the beetle Protaetia brevitarsis. Previously, we designed four 9-mer peptide analogues to optimize the balance between the hydrophobicity and cationicity of the peptides and to increase bacterial cell selectivity. Among them, 9Pbw2 has high antibacterial activity without cytotoxicity. The results obtained in previous study suggest that the bactericidal action of 9Pbw2 may be attributed to the inhibition of the functions of intracellular components after penetration of the bacterial cell membrane. In order to understand structure-activity relationships, we determined the three-dimensional structure of 9Pbw2 in 200 mM DPC micelle by NMR spectroscopy. 9Pbw2 has one hydrophobic turn helix from $Trp^3$ to $Arg^8$ and positively charged residues at the N- and C-terminus. This result suggested that positively charged residues from position at the C-terminus in 9Pbw2 may be important for the primary binding to the negatively charged phospholipid head groups in bacterial cell membranes and hydrophobic residues in the middle portion face toward the acyl chains of the hydrophobic lipid in the bacterial cell membrane.

• 대한화학회지
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• 제29권1호
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• pp.31-37
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• 1985

N-아세틸-ㅣ-페닐 알라닐-ㅣ-페닐 알라닌 메틸 에스테르(APhPhMe)와 N-아세틸-ㅣ-페닐 알라닌메틸에스테르(APhMe) 그리고 N-아세틸-ㅣ- 페닐알라닐-l-알라닌메틸에스테르(APhAlMe)를 모델화합물로 사용하여 단백질 변성을 연구하였다. APhPhMe는 압력이 증가하면 물에서의 용해도가 증가하였고 APhMe는 반대로 크게 감소하였지만 APhAlMe는 측정한 온도에서 거의 변화가 없었다. APhPhMe의 부피 변화는 20, 30, 40, 50$^{\circ}C$에서 각각 -0.9, -1.47, -1.09, -1.52 ml/mole이었고 APhMe는 20, 30, 40$^{\circ}C$에서 +6.0, +7.0, +7.5 ml/mole이었지만 APhAlMe는 세 온도 모두 0에 가까왔다. 이러한 결과를 소수성 상호작용과 펩티드 결합에 의한 수소결합으로 설명하였다. 즉 펩티드 결합만 존재하거나, 비교적 큰 소수성 작용기 1개와 펩티드 결합 1개가 동시에 있을 경우에는 펩티드 결합만 존재하거나, 비교적 큰 소수성 작용기 1개와 펩티드 결합 1개가 동시에 있을 경우에는 펩티드 결합사이의 수소결합이 소수성 상호 작용보다 우세하였고, 펩티드 결합과 소수성 작용기가 동시에 1개씩 증가할때는 소수성 상호작용이 우세한 것 같다.

• Bulletin of the Korean Chemical Society
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• 제28권10호
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• pp.1756-1762
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• 2007

Envelope proteins of virus contain a segment of hydrophobic amino acids, called as fusion peptide, which triggers membrane fusion by insertion into membrane and perturbation of lipid bilayer structure. Potential fusion peptide sequences have been identified in the middle of L or M proteins or at the N-terminus of S protein in the envelope of human hepatitis B virus (HBV). Two 16-mer peptides representing the N-terminal fusion peptide of the S protein and the internal fusion peptide in L protein were synthesized, and their membrane disrupting activities were characterized. The internal fusion peptide in L protein showed higher activity of liposome leakage and hemolysis of human red blood cells than the N-terminal fusion peptide of S protein. Also, the membrane disrupting activity of the extracellular domain of L protein significantly increased when the internal fusion peptide region was exposed to N-terminus by the treatment of V8 protease. These results indicate that the internal fusion peptide region of L protein could activate membrane fusion when it is exposed by proteolysis.

• BMB Reports
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• 제32권6호
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• pp.561-566
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• 1999

CA(1-8)-ME(1-12) [CA-ME], composed of cecropin A(1-8) and melittin(1-12), is a synthetic antimicrobial peptide having potent antibacterial and antitumor activities with minimal hemolytic activity. In order to investigate the effects of the flexible hinge sequence, Gly-Ile-Gly, of CA-ME on antibiotic activity, CA-ME and three analogues, CA-ME1, CA-ME2, and CA-ME3, were synthesized. The Gly-Ile-Gly sequence of Ca-ME was deleted in CA-ME1 and replaced with Pro and Gly-Pro-Gly in CA-ME2 and CA-ME3, respectively. CA-ME1 and CA-ME3 showed a significant decrease in antitumor activity and phospholipid vesicle-disrupting ability. However, CA-ME2 showed similar antitumor and vesicle-disrupting activities, as compared with CA-ME. These results suggest that the flexibility or ${\beta}$-turn induced by Gly-Ile-Gly or Pro in the central part of CA-ME may be important in the electrostatic interaction of the N-terminus cationic ${\alpha}$-helical region with the cell membrane surface and the hydrophobic interaction of the C-terminus amphipathic ${\alpha}$-helical region with the hydrophobic acyl chains in the cell membrane. CA-ME3 exhibited lower antitumor and vesicle-disrupting activities than CA-ME and CA-ME2. This result suggests that the excessive ${\beta}$-turn structure caused by the Gly-Pro-Gly sequence in CA-ME3 seems to interrupt ion channel/pore formation in the lipid bilayer. We concluded that the appropriate flexibility or bilayer. We concluded that the appropriate flexibility or ${\beta}$-turn structure provided by the central hinge is responsible for the effective antibiotic activity of the antimicrobial peptides with the helix-hinge-helix structure.