• 제목/요약/키워드: hydrophobic peptide

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Molecular Cloning and Structural Analysis of the Antibacterial Gene from the Common Cutworm, Spodoptera litura

  • Nam, Duk-Hwa;Tae, Gun-Sik
    • BMB Reports
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    • 제31권6호
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    • pp.536-541
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    • 1998
  • The cDNA clone encoding the antibacterial peptide (SL-1) was isolated from the fat body of the common cutworm, Spodoptera litura, immunized with E. coli K12. The primary structure analysis revealed that its deduced amino acid sequence showed the characteristics of the cecropin family antibacterial peptides and that the amino acid residues highly conserved in the antibacterial peptides from moths and flies were also conserved, implying that SL-1 was a cecropin-like, and especially cecropin B-like, peptide. The predicted secondary structure of the mature SL-1 consists of three domains: (i) an amphiphilic ${\alpha}$-helical domain (Ile-4 to Gly-18); (ii) the hinge region (Gly-23 and Pro-24); and (iii) a hydrophobic domain (Ala-25 to IIe-38).

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Influence of the Hydrophobic Amino Acids in the N- and C-Terminal Regions of Pleurocidin on Antifungal Activity

  • Lee, June-Young;Lee, Dong-Gun
    • Journal of Microbiology and Biotechnology
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    • 제20권8호
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    • pp.1192-1195
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    • 2010
  • To investigate the influence of the N- or C-terminal regions of pleurocidin (Ple) peptide on antifungal activity, four analogs partially truncated in the N- or C-terminal regions were designed and synthesized. Circular dichroism (CD) spectroscopy demonstrated that all the analogs maintained an alpha-helical structure. The antifungal susceptibility testing also showed that the analogs exhibited antifungal activities against human fungal pathogens, without hemolytic effects against human erythrocytes. The result further indicated that the analogs had discrepant antifungal activities [Ple>Ple (1-22)>Ple (4-25)>Ple (1- 19)>Ple (7-25)] and that N-terminal deletion affected the activities much more than C-terminal deletion. Hydrophobicity [Ple>Ple (1-22)>Ple (4-25)>Ple (1-19)> Ple (7-25)] was thought to have been one of the consistent factors that influenced these activity patterns, rather than the other primary factors like the helicity [Ple>Ple (4-25) >Ple (1-22)>Ple (1-19)>Ple (7-25)] or the net charge [Ple=Ple (4-25)=Ple (7-25)>Ple (1-22)=Ple (1-19)] of the peptides. In conclusion, the hydrophobic amino acids in the N-terminal region of Ple is more crucial for antifungal activity than those in the C-terminal region.

3D Quantitative and Qualitative Structure-Activity Relationships of the δ -Opioid Receptor Antagonists

  • Chun, Sun;Lee, Jee-Young;Ro, Seong-Gu;Jeong, Ki-Woong;Kim, Yang-Mee;Yoon, Chang-Ju
    • Bulletin of the Korean Chemical Society
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    • 제29권3호
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    • pp.656-662
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    • 2008
  • Antagonists of the d -opioid receptor are effective in overcoming resistance against analgesic drugs such as morphine. To identify novel antagonists of the d -opioid receptor that display high potency and low resistance, we performed 3D-QSAR analysis using chemical feature-based pharmacophore models. Chemical features for d -opioid receptor antagonists were generated using quantitative (Catalyst/HypoGen) and qualitative (Catalyst/HipHop) approaches. For HypoGen analysis, we collected 16 peptide and 16 non-peptide antagonists as the training set. The best-fit pharmacophore hypotheses of the two antagonist models comprised identical features, including a hydrophobic aromatic (HAR), a hydrophobic (HY), and a positive ionizable (PI) function. The training set of the HipHop model was constructed with three launched opioid drugs. The best hypothesis from HipHop included four features: an HAR, an HY, a hydrogen bond donor (HBD), and a PI function. Based on these results, we confirm that HY, HAR and PI features are essential for effective antagonism of the d -opioid receptor, and determine the appropriate pharmacophore to design such antagonists.

Effect of Double Replacement of L-Pro, D-Pro, D-Leu or Nleu in Hydrophobic Face of Amphipathic α-Helical Model Antimicrobial Peptide on Structure, Cell Selectivity and Mechanism of Action

  • Shin, Song Yub
    • Bulletin of the Korean Chemical Society
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    • 제35권11호
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    • pp.3267-3274
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    • 2014
  • In order to investigate the effects of the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu (the peptoid residue for Leu) in the hydrophobic face (positions 9 and 13) of amphipathic ${\alpha}$-helical non-cell-selective antimicrobial peptide $L_8K_9W_1$ on the structure, cell selectivity and mechanism of action, we synthesized a series of $L_8K_9W_1$ analogs with double replacement of $\small{L}$-Pro, $\small{D}$-Pro, $\small{D}$-Leu or Nleu in the hydrophobic face of $L_8K_9W_1$. In this study, we have confirmed that the double replacement of $\small{L}$-Pro, $\small{D}$-Pro, or Nleu in the hydrophobic face of $L_8K_9W_1$ let to a great increase in the selectivity toward bacterial cells and a complete destruction of ${\alpha}$-helical structure. Interestingly, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu preferentially interacted with negatively charged phospholipids, but unlike $L_8K_9W_1$ and $L_8K_9W_1$-$\small{D}$-Leu, they did not disrupt the integrity of lipid bilayers and depolarize the bacterial cytoplasmic membrane. These results suggested that the mode of action of $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu involves the intracellular target other than the bacterial membrane. In particular, $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu had powerful antimicrobial activity (MIC range, 1 to $4{\mu}M$) against methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Pseudomonas aeruginosa (MDRPA). Taken together, our results suggested that $L_8K_9W_1$-$\small{L}$-Pro, $L_8K_9W_1$-$\small{D}$-Pro and $L_8K_9W_1$-Nleu with great cell selectivity may be promising candidates for novel therapeutic agents, complementing conventional antibiotic therapies to combat pathogenic microorganisms.

Solution Dynamics Studies for the Lck SH2 Domain Complexed with Peptide and Peptide-Free Forms

  • Yoon, Jeong-Hyeok;Chi, Myung-Whan;Yoon, Chang-No;Park, Jongsei
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1995년도 춘계학술대회
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    • pp.81-81
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    • 1995
  • It is well known that Src Homology 2(SH2) domain in many intracellular signal transduction proteins is very important. The domain has about 100 amino acid residues and bind phosphotyrosine-containing peptide with high affinity and specificity. Lck SH2 domain is a Src-like, lymphocyte-specific tyrosine kinase. An 11-residue phosphopeptide derived from the hamster polvoma middle-T antigen, EPQp YEEIPIYL, binds with an 1 nM dissociation constant to Lck SH2 domain. And it is known that the phosphotyrosine and isoleucine residues of the peptide are tightly bound by two well-defined pockets on Lck SH2 domain's surface. To investigate the conformational changes during complexation of SH2 domain with phosphopeptide we have performed the molecular dynamics simulation for Lck SH2 domain with peptide and peptide-free form at look in aqueous solution. More than 3000 water molecules were incorporated to solvate Lck SH2 domain and peptide. Periodic boundary condition has been applied in molecular dynamics simulation. Data analysis with the results of that simulation shows that the phosphopeptide makes primary interaction with the Lck SH2 domain at six central residues, The comparison of the complexed and uncomplexed SH2 domain structures in solution has revealed only relatively small change. But the hydrophilic and hydrophobic pockets in the protein surface show the conformational changes in spite of the small structural difference between the complex and peptide-free forms.

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가토 신장기능에 미치는 Pro-Atrial Natriuretic Peptide의 영향 (Effects of Intrarenal Arterial Infusion of Pro-Atrial Natriuretic Peptides on Renal Function in Unanesthetized Rabbits)

  • 이정은;조경우;김선희
    • The Korean Journal of Physiology
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    • 제24권1호
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    • pp.131-144
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    • 1990
  • It is well known that the atrial natriuretic peptide (ANP) has a prepro-hormone of 151 amino-acids which loses their hydrophobic signal peptide to form 126 amino acid prohormone. The whole prohormone is released and then cleaved by proteases into more than one circulating forms. Recently, Winters et al. (1988a, b) reported that high concentrations of N-terminal fragments of prepro-ANP $(26{\sim}55),\;(56{\sim}92)\;and\;(104{\sim}123)$ were detected in human plasma. However, their physiological roles have not been established. The present study was conducted to determine whether the N-terminal fragments of pro-ANP have any effect on the renal function and to compare the effect with those of G-terminal fragments of pro-ANP The results indicate that intrarenal arterial infusions of prepro-ANP $(26{\sim}41),\;(26{\sim}55),\;(56{\sim}92)\;and\;(104{\sim}123)$ induced no significant changes in renal function. Whereas ${\alpha}-human$ ANP $(prepro-ANP,\;124{\sim}151)$ and pro-ANP caused a significant increase in urine volume, renal plasma flow, glomerular filtration rate, urinary excretions of sodium, chloride and potassium, and fractional excretion of sodium. These results suggest that the N-terminal fragments of pro-ANP are ineffective, while the C-terminal fragments retain the natriuretic and diuretic activities.

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Structure-Function of the TNF Receptor-like Cysteine-rich Domain of Osteoprotegerin

  • Shin, Joon;Kim, Young-Mee;Li, Song-Zhe;Lim, Sung-Kil;Lee, Weontae
    • Molecules and Cells
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    • 제25권3호
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    • pp.352-357
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    • 2008
  • Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits osteoclastogenesis and is closely associated with bone resorption processes. We have designed and determined the solution structures of potent OPG analogue peptides, derived from sequences of the cysteine-rich domain of OPG. The inhibitory effects of the peptides on osteoclastogenesis are dose-dependent ($10^{-6}M-10^{-4}M$), and the activity of the linear peptide at $10^{-4}M$ is ten-fold higher than that of the cyclic OPG peptide. Both linear and cyclic peptides have a ${\beta}$-turn-like conformation and the cyclic peptide has a rigid conformation, suggesting that structural flexibility is an important factor for receptor binding. Based on structural and biochemical information about RANKL and the OPG peptides, we suggest that complex formation between the peptide and RANKL is mediated by both hydrophobic and hydrogen bonding interactions. These results provide structural insights that should aid in the design of peptidyl-mimetic inhibitors for treating metabolic bone diseases caused by abnormal osteoclast recruitment.

Ku80의 DNA-PKcs 결합부위 합성 Peptide 투여에 의한 유방암세포의 DNA-dependent protein kinase 억제 효과 (Effect on the Inhibition of DNA-PK in Breast Cancer Cell lines(MDA-465 and MDA-468) with DNA-PKcs Binding Domain Synthetic Peptide of Ku80)

  • 김충희;김태숙;문양수;정장용;강정부;김종수;강명곤;박희성
    • 한국임상수의학회지
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    • 제21권3호
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    • pp.253-258
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    • 2004
  • DNA double-strand break (DSB) is a serious treat for the cells including mutations, chromosome rearrangements, and even cell death if not repaired or misrepaired. Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) bound to double strand DNA breaks are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and the interaction is essential for DNA-dependent protein kinase (DNA-PK) activity. The Ku80 mutants were designed to bind Ku70 but not DNA end binding activity and the peptides were treated in breast cancer cells for co-therapy strategy to see whether the targeted inhibition of DNA-dependent protein kinase (DNA-PK) activity sensitized breast cancer cells to ionizing irradiation or chemotherapy drug to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. We designed domains of Ku80 mutants, 26 residues of amino acids (HN-26) as a control peptide or 38 (HNI-38) residues of amino acids which contain domains of the membrane-translocation hydrophobic signal sequence and the nuclear localization sequence, but HNI-38 has additional twelve residues of peptide inhibitor region. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, resulting in inactivation of DNA-PK complex activity in breast cancer cells (MDA-465 and MDA-468). Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to irradiation or chemotherapy drugs. The growth of breast cancer cells was also inhibited. These results demonstrate the possibility of synthetic peptide to apply breast cancer therapy to induce apoptosis of cancer cells.

Influences of Hinge Region of a Systhetic Antimicrobial Peptide, Cecropin A(1-13)-Melittin(1-13) Hybrid on Antibiotic Activity

  • 신송엽;강주현;이동건;장소윤;서무열;김길룡;함경수
    • Bulletin of the Korean Chemical Society
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    • 제20권9호
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    • pp.1078-1084
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    • 1999
  • A synthetic cecropin A(1-13)-melittin(1-13) [CA-ME] hybrid peptide was known to be an antimicrobial peptide having strong antibacterial, antifungal and antitumor activity with minimal cytotoxic effect against human erythrocyte. Analogues were synthesized to investigate the influences of the flexible hinge region of CA-ME on the antibiotic activity. Antibiotic activity of the peptides was measured by the growth inhibition against bac-terial, fungal and tumor cells and vesicle-aggregating or disrupting activity. The deletion of Gln-Gly-Ile (P1) or Gly-Gln-Gly-Ile-Gly (P3) from CA-ME brought about a significant decrease on the antibiotic activities. In contrast, Gly-Ile-Gly deletion (P2) from CA-ME or Pro insertion (P5) instead of Gly-Gln-Gly-Ile-Gly of CA-ME retained antibiotic activity. This result indicated that the flexible hinge or β-bend structure provided by Gly-Gln-Gly-Ile-Gly, Gln-Gly, or Pro in the central region of the peptides is requisite for its effective antibiotic activity and may facilitate easily the hydrophobic C-terminal region of the peptide to penetrate the lipid bilayers of the target cell membrane. In contrast, P4 and P6 with Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central region of the peptide caused a drastic reduction on the antibiotic activities. This result suggested that the con-secutive β-bend structure provided by Gly-Gln-Gly-Pro-Gly or Gly-Gln-Pro in the central hinge region of the peptide seems to interrupt the ion channel/pore formation on the target cell membranes.

Thermodynamics of the binding of Substance P to lipid membranes

  • Lee, Woong Hyoung;Kim, Chul
    • 분석과학
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    • 제30권2호
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    • pp.89-95
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    • 2017
  • The thermodynamic functions for the binding of the peptide Substance P (SP) on the surface of lipid vesicles made of various types of lipids were obtained by using isothermal titration calorimetry. The reaction enthalpies measured from the experiments were -0.11 to $-4.5kcal\;mol^{-1}$. The sizes of the lipid vesicles were measured with dynamic light scattering instrument in order to get the correlation between the reaction enthalpies and the vesicle sizes. The bindings of SP on the lipid vesicles with diameter of 37 to 108 nm were classified into the enthalpy-driven reaction or the entropy-driven reaction according to the size of the lipid vesicles. For the enthalpy-driven binding reaction, the significance of the electrostatic interactions between SP and lipid molecules was affirmed from the experimental results of the DMPC/DMPG/DMPH and DMPC/DMPS/DMPH vesicles as well as the importance of the hydrophobic interactions between hydrophobic groups of SP and lipid molecules.