제43차 분과 세미나 공고
2005.02.03 조회 수 : 5336

대한화학회 의약화학분과 회원께,

이미 예고드린 대로, 분과회의 새해 첫 모임으로, 아래와 같이 제43차 대한화학회 의약화학분과 세미나를 개최합니다. 산학연 협력을 보다 활성화하기 위한 시도로, 주요 제약산업의 연구현장에서 세미나를 여는 취지를 이해하시고 많은 참석 있으시기 바랍니다.

- 일시: 2005년 2월 25 일 (금) 오후 3시30분 - 8시
- 장소: 종근당 중앙연구소 (아래 약도 참조)
- 등록비: 2 만원

- 일정

15:30 - 16:00 등록

16:00 - 17:00 추현아 박사 (한국과학기술연구원)

1. Title : Synthesis and anti-HIV activity of thionucleosides

2. Abstract :
Viral disease continues to be one of the major human health problems. Currently, seven anti-HIV nucleoside analogs and two anti-HBV nucleosides have been approved by the FDA, but their therapeutic limitations such as toxicity and emergence of resistant viral strains prompted us to discover safer and more effective antiviral nucleoside analogs. For this purpose, various thionucleosides were synthesized and biologically evaluated against wild type HIV-1 and lamivudine-resistant HIV strains. Among those, L-2’, 3’-didehydro-2’,3’-dideoxy-2’-fluoro-4’-thiocytidine (L-2’F-4’S-d4C) showed the most potent antiviral activity against wild type HIV-1 with EC50 of 0.12 mM without significant cytotoxicity up to 100 mM in various human cell lines. However, L-2’F-4’S-d4C showed significant cross-resistance against the clinically important lamivudine-resistant HIV strains, of which mechanism could be partially explained by molecular modeling studies using the crystal structure of HIV-1 reverse transcriptase (1rtd) in Sybyl program. Design, synthesis, biological evaluation and molecular modeling studies of various novel antiviral nucleoside analogs will be discussed.

3. 학력 및 경력

1993년 서울대 화학과 졸업
1996년 서울대 화학과 석사 (지도교수: 홍종인 교수)
1998년 서울대 화학과 박사 수료
2003년 미국 조지아대 약대 박사 (Prof. David C.K. Chu)
2003년-2004년 Post Doc. at U.C. San Diego
2005년 1월~ 한국과학기술연구원에 연구원으로 근무시작

17:00 - 18:00 정유훈 박사

1. Titlte: Design, Synthesis and Biological Evaluation of de novo Purine Biosynthesis Pathway Inhibitors

2. Abstract :

The inhibition of folate-dependent enzymes has been a central focus of therapeutic research for over 50 years (antimetabolites) and has provided a number of clinically useful anticancer agents. The discovery that Lometrexol [(6R)-DDATHF] is an efficacious antitumor agent that inhibits de novo purine synthesis and acts as a potent inhibitor of glycinamide ribonucleotide formyltransferase (GAR Tfase), established this enzyme as an important therapeutic target for antineoplastic intervention. Highlights of our GAR Tfase inhibitor studies include the discovery of: i) 10-CF3CO-DDACTHF as the most potent and selective GAR Tfase inhibitor disclosed to date (Ki = 15 nM) and an exceptional inhibitor of CCRF–CEM cell growth (IC50 = 16 nM), ii) its γ-carboxamide derivative which represents an exceptionally potent non-polyglutamylatable GAR Tfase inhibitor that may reduce the typical dose-limiting cumulative toxicity of such folate analogs because its functional activity is not dependent on FPGS polyglutamation (Ki = 56 nM, IC50 = 300 nM, IC50 CCRF–CEM/FPGS– = 500 nM), and iii) 10-MeS-DDACTHF which constitutes an unusually efficacious GAR Tfase inhibitor being 3´ more potent than Lometrexol in functional assays (Ki = 250 nM, IC50 = 80–100 nM, CCRF–CEM).
We also targeted inosine monophosphate cyclohydrolase (IMPCH), which promotes the conversion of N-formyl-aminoimidazole carboxamide ribonucleotide (FAICAR) to IMP in the final step of the purine biosynthesis. Consequently, it is an enzyme with which we necessarily focused on substrate-based inhibitors. The most successful of the designs to date enlisted the sulfonyldiamides as a mimic of the intermediate in the IMP cyclization/dehydration reaction. Beautifully, not only were the nucleoside and nucleotide analogs and effective inhibitors of IMPCH, but the simple heterocycle proved to be an even more potent inhibitor (Ki = 129 nM).

3. 학력 및 경력

1994년 서울대 화학과 학사
1997년 서울대 화학과 석사 (지도교수: 이은 교수)
2003년 미국 조지아 대학 약대 박사 (Prof. David C.K. Chu)
2003년-2005년 Post Doc. at The Scripps Research Institute
2005년 3월~ 건국대학교 생명환경과학대학 응용생명과학부 분자생물공학과 조교수 근무 예정

18:30 - 20:00 저녁 식사

연락처 안순길 (종근당, 042-529-3107)
최경일 (키스트, 02-958-5166)

대한화학회 의약화학분과 회장 장문호