• Title/Summary/Keyword: Combinatorial library

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Resurrection of antibody as a therapeutic drug (항체 : 치료제로서의 부활)

  • Chung, Hong Keun;Chung, Junho
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.7-13
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    • 2001
  • Currently 18 monoclonal antibodies were approved by FDA for inj ection into humans for therapeutic or diagnostic purpose. And 146 clinical trials are under way to evaluate the efficacy of monoclonal antibodies as anti-cancer agents, which comprise 9 % of clinical trials in cancer therapy field. When considering a lot of disappointment and worries existed in this field during the past 15 years, this boom could be called as resurrection. Antibodies have several merits over small molecule drug. First of all it is easier and faster in development, as proper immunization of the target proteins usually raises good antibody response. The side effects of antibodies are more likely to be checked out in immunohistomchemical staining of whole human tissues. Antibody has better pharmacokinetics, which means a longer half-life. And it is non-toxic as it is purely a "natural drug. Vast array of methods was developed to get the recombinant antibodies to be used as drug. The mice with human immunoglobulin genes were generated. Fully human antibodies can be developed in fast and easy way from these mice through immunization. These mice could make even human monoclonal antibodies against any human antigen like albumin. The concept of combinatorial library was also actively adopted for this purpose. Specific antibodies can be screened out from phage, mRNA, ribosomal library displaying recombinant antibodies like single chain Fvs or Fabs. Then the coding genes of these specific antibodies are obtained from the selected protein-gene units, and used for industrial scale production. Both $na\ddot{i}ve$ and immunized libraries are proved to be effective for this purpose. In post-map arena, antibodies are receiving another spotlight as molecular probes against numerous targets screened out from functional genomics or proteomics. Actually many of these antibodies used for this purpose are already human ones. Through alliance of these two actively growing research areas, antibody would play a central role in target discovery and drug development.

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An Integer Programming-based Local Search for the Set Covering Problem (집합 커버링 문제를 위한 정수계획법 기반 지역 탐색)

  • Hwang, Jun-Ha
    • Journal of the Korea Society of Computer and Information
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    • v.19 no.10
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    • pp.13-21
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    • 2014
  • The set covering problem (SCP) is one of representative combinatorial optimization problems, which is defined as the problem of covering the m-rows by a subset of the n-columns at minimal cost. This paper proposes a method utilizing Integer Programming-based Local Search (IPbLS) to solve the set covering problem. IPbLS is a kind of local search technique in which the current solution is improved by searching neighborhood solutions. Integer programming is used to generate neighborhood solution in IPbLS. The effectiveness of the proposed algorithm has been tested on OR-Library test instances. The experimental results showed that IPbLS could search for the best known solutions in all the test instances. Especially, I confirmed that IPbLS could search for better solutions than the best known solutions in four test instances.

sanN Encoding a Dehydrogenase is Essential for Nikkomycin Biosynthesis in Streptomyces ansochromogenes

  • Ling, Hong-Bo;Wang, Guo-Jun;Li, Jin-E;Tan, Hua-Rong
    • Journal of Microbiology and Biotechnology
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    • v.18 no.3
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    • pp.397-403
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    • 2008
  • Nikkomycins are a group of peptidyl nucleoside antibiotics with potent fungicidal, insecticidal, and acaricidal activities. sanN was cloned from the partial genomic library of Streptomyces ansochromogenes 7100. Gene disruption and complementation analysis demonstrated that sanN is essential for nikkomycin biosynthesis in S. ansochromogenes. Primer extension assay indicated that sanN is transcribed from two promoters (sanN-P1 and sanN-P2), and sanN-P2 plays a more important role in nikkomycin biosynthesis. Purified recombinant SanN acts as a dehydrogenase to convert benzoate-CoA to benzaldehyde in a random-order mechanism in vitro, with respective $K_{cat}/K_m$$ values of $3.8mM^{-1}s^{-1}\;and\;12.0mM^{-1}s^{-1}$ toward benzoate-CoA and NADH, suggesting that SanN catalyzes the formation of picolinaldehyde during biosynthesis of nikkomycin X and Z components in the wild-type stain. These data would facilitate us to understand the biosynthetic pathway of nikkomycins and to consider the combinatorial synthesis of novel antibiotic derivatives.

The Safety Evaluation of a Potent Angiogenic Activator, Synthetic Peptide (SFKLRY-NH2) for the Skin Application

  • Kim, Dong-Ha;Lim, Yun-Young;Kim, Hyeong-Mi;Kim, So-Young;Kim, Beom-Joon;Park, Sung-Gil;Lee, Tae-Hoon;Cho, Soo-Muk
    • Toxicological Research
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    • v.28 no.1
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    • pp.51-56
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    • 2012
  • A novel synthetic hexapeptide (SFKLRY-$NH_2$) that displays angiogenic activity has been identified by positional scanning of a synthetic peptide combinatorial library (PS-SPCL). This study was carried out to investigate the irritation of the SFKLRY-$NH_2$ on the skin. The tests were performed on the basis of Korea Food and Drug Administration (KFDA) guidelines. In results, cell toxicity is not appeared for SFKLRY-$NH_2$ in HaCaT cells and B16F10 cells. SFKLRY-$NH_2$ induced no skin irritation at low concentration ($10{\mu}m$), mild irritation at high concentration (10mM). We consider that this result is helpful for saying about the safety of SFKLRY-$NH_2$ in clinical use.

Construction of a Focused Library of 2-benzylimino-1,3-thiazolines and Their Fungicidal Activities (2-벤질이미노-1,3-티아졸린 유도체의 집중 라이브러리의 구축 및 이들의 살균활성)

  • Park, Ik-Kyu;Lim, Chul-Soo;Nam, Kee-Dal;Shin, Dong-Yoon;Choi, Kyung-Ja;Cho, Kwang-Yun;Hahn, Hoh-Gyu
    • The Korean Journal of Pesticide Science
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    • v.10 no.2
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    • pp.149-152
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    • 2006
  • Construction of focused library of 2-benzylimino-1,3-thiazolines 7 through molecular modification of 3-alkyl-2-phenylimino-1,3-thiazolines 1 which showed selective fungicidal activity against rice blast and their fungitoxic activity against 6 kinds of typical plant diseases was described. Fifty four compounds of focused library of 2-benzylimino-1,3-thiazolines 7 were synthesized from the reaction of the corresponding $\gamma$-chloroacetoacetanilides 6 with N-benzyl thioureas 5 by parallel synthetic methodology. As results of fungicidal screening against the typical plant diseases, twenty eight kinds of 7 at 100 ${\mu}g$ $mL^{-1}$ showed the control value over 50% against tomato late blight.

Synthesis and Luminescent Properties of Y(As, Nb, P, V)O4:Eu3+ Red Phosphors by Combinatorial Chemistry Method (조합화학을 이용한 Y(As, Nb, P, V)O4:Eu3+ 적색형광체의 합성 및 광 특성 분석)

  • Jeon, Il Un;Son, Gi Seon;Park, Hui Dong;Ryu, Seung Gon
    • Journal of the Korean Chemical Society
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    • v.45 no.6
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    • pp.577-588
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    • 2001
  • Eu doped YRO$_4$ (R=As, Nb, P, V) red phosphors were prepared by the combinatorial chemistry method. The quaternary material library of tetrahedron-type composition array was designed to investigate the luminescence of the host material under UV and VUV excitations (254, 147 nm). The photoluminescent characteristics of the samples were comparable to the commercially available red phosphors such as (Y, Gd)BO$_3$: $Eu^{3+}$ and Y$_2$O$_3$: In view of the luminescence yield, V rich region was found to be optimum under UV excitation. But the results under VUV excitation were different from those of UV excitation, the samples of the composition containing a large amount of P shows the highest luminescence. Especially, higher luminescence was obtained in $Y_{0.9}$(A$S_{0.06}$N$B_{0.06}P_{0.83}V_{0.06}$) O$_4$: $Eu_{0.1}$ phosphors than commercial (Y, Gd)BO$_3$red phosphors under 147 nm excitation.

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Monitoring of Cleavage Preference for Caspase-3 Using Recombinant Protein Substrates

  • Park, Kyoung-Sook;Yi, So-Yeon;Kim, Un-Lyoung;Lee, Chang-Soo;Chung, Jin-Woong;Chung, Sang-J.;Kim, Moon-Il
    • Journal of Microbiology and Biotechnology
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    • v.19 no.9
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    • pp.911-917
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    • 2009
  • The apoptotic caspases have been classified in accordance with their substrate specificities, as the optimal tetrapeptide recognition motifs for a variety of caspases have been determined via positional scanning substrate combinatorial library technology. Here, we focused on two proteolytic recognition motifs, DEVD and IETD, owing to their extensive use in cell death assay. Although DEVE and IETD have been generally considered to be selective for caspase-3 and -8, respectively, the proteolytic cleavage of these substrates does not display absolute specificity for a particular caspase. Thus, we attempted to monitor the cleavage preference for caspase-3, particularly using the recombinant protein substrates. For this aim, the chimeric GST:DEVD:EGFP and GST:IETD:EGFP proteins were genetically constructed by linking GST and EGFP with the linkers harboring DEVD and IETD. To our best knowledge, this work constitutes the first application for the monitoring of cleavage preference employing the recombinant protein substrates that simultaneously allow for mass and fluorescence analyses. Consequently, GST:IETD:EGFP was cleaved partially in response to caspase-3, whereas GST:DEVD:EGFP was completely proteolyzed, indicating that GST:DEVD:EGFP is a better substrate than GST:IETD:EGFP for caspase-3. Collectively, using these chimeric protein substrates, we have successfully evaluated the feasibility of the recombinant protein substrate for applicability to the monitoring of cleavage preference for caspase-3.

Construction of voxel head phantom and application to BNCT dose calculation (Voxel 머리팬텀 제작 및 붕소중성자포획요법 선량계산에의 응용)

  • Lee, Choon-Sik;Lee, Choon-Ik;Lee, Jai-Ki
    • Journal of Radiation Protection and Research
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    • v.26 no.2
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    • pp.93-99
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    • 2001
  • Voxel head phantom for overcoming the limitation of mathematical phantom in depleting anatomical details was constructed and example dose calculation for BNCT was performed. The repeated structure algorithm of the general purpose Monte Carlo code, MCNP4B was applied for yokel Monte Carlo calculation. Simple binary yokel phantom and combinatorial geometry phantom composed of two materials were constructed for validating the voxel Monte Carlo calculation system. The tomographic images of VHP man provided by NLM(National Library of Medicine) were segmented and indexed to construct yokel head phantom. Comparison of doses for broad parallel gamma and neutron beams in AP and PA directions showed decrease of brain dose due to the attenuation of neutron in eye balls in case of yokel head phantom. The spherical tumor volume with diameter, 5cm was defined in the center of brain for BNCT dose calculation in which accurate 3 dimensional dose calculation is essential. As a result of BNCT dose calculation for downward neutron beam of 10keV and 40keV, the tumor dose is about doubled when boron concentration ratio between the tumor to the normal tissue is $30{\mu}g/g$ to $3{\mu}g/g$. This study established the voxel Monte Carlo calculation system and suggested the feasibility of precise dose calculation in therapeutic radiology.

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Screening of Eu3+-and Tb3+-Activated Phosphors for PDP in the System of CaO-Gd2O3-Al2O3 (CaO-Gd2O3-Al2O3계에서의 PDP용 Eu3+와 Tb3+ 활성 형광체의 탐색)

  • Park, Sang-Mi;Kim, Chang-Hae;Park, Hui-Dong;Jang, Ho-Gyeom;Park, Jun-Taek
    • Journal of the Korean Chemical Society
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    • v.46 no.4
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    • pp.336-345
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    • 2002
  • In this study, we have screened $Eu^{3+}$- and $Tb^{3+}$-activated candidate phosphors for PDP in the sys-tems of CaO-Gd$_2$O$_3$-Al$_2$O$_3$ by combinatorial chemistry and investigated the synthetic temperature, optimum com-position and luminescent properties about the candidate phosphors. To construct the emission intensity library by VUV PL, we have synthesized 210 different compositional samples using a polymerized-complex method. Good luminescent samples were identified by X-ray diffraction method. $Ca_$\alpha$$G$d_{0.95-$\alpha$-$\beta$}Al_$\beta$O_$\delta$$ : Eu(0.02< $\alpha$+$\beta$ <0.04) phos-phors screened as a red phosphor have good color purity than commercial phosphor. In the candidate phosphors of CaGdAl$_3O_7$ : Tb, Ca$Al_{12}O_{19}$ : Tb, Gd$_4$Al$_2O_9$ : Tb, and Gd$_3Al_5O_{12}$ : Tb CaGdAl$_3O_7$ : Tb, and Ca$Al_{12}O_{19}$ : Tb have shorter decay time than commercial phosphor.

Generation of single stranded DNA with selective affinity to bovine spermatozoa

  • Vinod, Sivadasan Pathiyil;Vignesh, Rajamani;Priyanka, Mani;Tirumurugaan, Krishnaswamy Gopalan;Sivaselvam, Salem Nagalingam;Raj, Gopal Dhinakar
    • Animal Bioscience
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    • v.34 no.10
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    • pp.1579-1589
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    • 2021
  • Objective: This study was conducted to generate single stranded DNA oligonucleotides with selective affinity to bovine spermatozoa, assess its binding potential and explore its potential utility in trapping spermatozoa from suspensions. Methods: A combinatorial library of 94 mer long oligonucleotide was used for systematic evolution of ligands by exponential enrichment (SELEX) with bovine spermatozoa. The amplicons from sixth and seventh rounds of SELEX were sequenced, and the reads were clustered employing cluster database at high identity with tolerance (CD-HIT) and FASTAptamer. The enriched nucleotides were predicted for secondary structures by Mfold, motifs by Multiple Em for Motif Elicitation and 5' labelled with biotin/6-FAM to determine the binding potential and binding pattern. Results: We generated 14.1 and 17.7 million reads from sixth and seventh rounds of SELEX respectively to bovine spermatozoa. The CD-HIT clustered 78,098 and 21,196 reads in the top ten clusters and FASTAptamer identified 2,195 and 4,405 unique sequences in the top three clusters from the sixth and seventh rounds, respectively. The identified oligonucleotides formed secondary structures with delta G values between -1.17 to -26.18 kcal/mol indicating varied stability. Confocal imaging with the oligonucleotides from the seventh round revealed different patterns of binding to bovine spermatozoa (fluorescence of the whole head, spot of fluorescence in head and mid- piece and tail). Use of a 5'-biotin tagged oligonucleotide from the sixth round at 100 pmol with 4×106 spermatozoa could trap almost 80% from the suspension. Conclusion: The binding patterns and ability of the identified oligonucleotides confirms successful optimization of the SELEX process and generation of aptamers to bovine spermatozoa. These oligonucleotides provide a quick approach for selective capture of spermatozoa from complex samples. Future SELEX rounds with X- or Y- enriched sperm suspension will be used to generate oligonucleotides that bind to spermatozoa of a specific sex type.