• Biomolecules & Therapeutics
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• 제2권2호
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• pp.155-160
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• 1994

Human immunodeficiency virus type 1 (HIV-1) protease is essential for the replication of the virus and it is therefore an attractive target for antiviral drugs of HIV-1. Several dipeptide isosteres containing 2-isoxazoline or $\alpha$-hydroxy ketomethylene have been synthesized and their inhibitory effects on the HIV-1 protease examined. The enzymatically active HIV-1 protease was purified to homogeniety from E. coli transformed with a recombinant plasmid (pMAL-pro) containing the entire gene encoding the protease. The purified protease had the substrate specificity with Km value of 9.8$\mu$M when an undecapeptide His-Lys-Ala-Arg-Val-Leu-(p-nitro)Phe-Glu-Ala-Nle-Ser-amide was used as a substrate, and the products from the substrate after specific cleavage by HIV-1 protease were analyzed by HPLC. The synthetic compounds containing dipeptide isosteres showed specific inhibitory effects while a dipeptide isostere containing an isoxazoline ring inhibited the HIV-1 protease competitively with Ki value of 500 $\mu$M. Even if the inhibition effects of HIV-1 protease were not very high, these novel dipeptide isosteres can be used as key structural moieties for developing specific inhibitors of HIV-1 protease.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.219-219
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• 1994

고혈압 치료제의 하나로 사용되고 있는 Angiotensin Converting Enzymc (ACE) 억제제를 본 실험실에서 개발한 $\alpha$-hydroxy ketomethylene isostere를 핵심요소로 하여 합성하였다. 합성한 억제제 후보물질의 억제효과는 Rabbit Ling으로 부터 단리된 ACE를 사용하여 분광학적인 방법에 의해 결정되었다. 화합물 1은 우수한 억제효과를 나타내었다.