Seminar

Seminar

[세미나공지] 12월 11일(목)

  • POSTED DATE : 2014-12-12
  • WRITER : 관리자
  • HIT : 2780
  • DATE : 2014-12-11
  • PLACE : 화학관 330226호

 안녕하세요.


다음주 정규세미나는 목요일(12월 11일) 4시 30분부터 330226호에서 더블헤더로 진행됩니다.               

많은 참석 부탁드립니다.

 
감사합니다.       


 

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정규세미나1.

 

제  목 : Molecular basis of unexpected enantioselective resolutions of aminoalcohols by lipase and

            Development of novel  Enzyme from high-throughput screening of metagenomic library

 

연  사 : 이혁 박사(한국화학연구원)

 

일  시 : 2014년 12월 11일(목) 오후 4시 30분


장  소 : 화학관 세미나실 (330226호실)

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Molecular basis of unexpected enantioselective resolutions of aminoalcohols by lipase and Development of novel Enzyme from high-throughput screening of metagenomic library

 

    

      1)  Lipases

     Lipases (EC 3.1.1.3) are one of the most widely used biocatalysts in the fields of academic and industrial research because of their high levels of thermal and chemical stability. Most lipases resolve secondary alcohols in accordance with the “Kazlauskas rule” to give the R-enantiomer. In a similar manner toother lipases, Candida rugosa lipase (CRL) exhibits R-enantioselectivity towards2-heptanol, although the enantiomeric ratio (E)is low (E = 1.6). However, it has been observed unexpected enantioselectivity (i.e., S-enantioselectivity) (E = 58)of CRL towards N-Boc-4-aminobutan-2-ol, which has asimilar chain length to 2-heptanol. To develop a deeper understanding of themolecular basis for this unusual enantioselectivity, we have conducted a series of molecular modeling and substrate engineering experiments. The results of thesecomputational and experimental analyses indicated that a hydrogen bond between the Ser450 residue and the nitrogen atom of the carbamate group is critical to stabilize the transition state of the S-enantiomer.



      2)  Hab Mutase

   

We have established a simple and efficient high-throughput screening (HTS) system to identify novel isomerization activity for aromatic compounds from soil metagenomic libraries. Based on this HTS approach, we have discovered and characterized a novel enzyme among 740,000 clones in metagenomic libraries. Then we attempted to develop a novel biotransformation reaction for organic synthesis. This enzyme was overexpressed in E. coli and tested for a biotransformation reaction in various reaction conditions for an optimization. The combination of reduction and isomerization was designed for an easy use of this reaction, and we prepared whole E. coli cell biocatalyst having dual activity. Using this biocatalyst, multi-step reaction with diverse aromatic compounds was successfully carried out to give rise to good yields. I will discuss the whole process from finding a novel enzyme to developing a new biotransformation.


 

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정규세미나2.

 

제  목 : EGFR Inhibitors for Lung Cancer


연  사 : 이광호 박사(한국화학연구원)

 

일  시 : 2014년 12월 11일(목) 오후 5시 30분


장  소 : 화학관 세미나실 (330226호실)

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EGFR Inhibitors for Lung Cancer

   

Erlotinib (Tarceva) & Gefitinib (Iressa) are currently in clinic use as epidermal growth factor receptor (EGFR) kinase inhibitors for non-small-cell lung cancer (NSCLC).  However, their clinical efficacy is limited by both their mechanism-based toxicity and the development of drug-resistance mutations, including the gatekeeper T790M mutation.  Unlike their quinazoline-based core scaffold, a new pyrimidine-based irreversible inhibitor has been identified for the EGFR gatekeeper T790M mutant specific activities.  These pyrimidine-based EGFR inhibitors may provide improved therapeutic window and more effective clinical treatment for NSCLC patients.