Asano T, Matsuoka K, Hida T, Kobayashi M, Kitamura Y, Hayakawa T, Iinuma S, Kakinuma A, Kato K
Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
J Antibiot (Tokyo). 1994 May;47(5):557-65. doi: 10.7164/antibiotics.47.557.
Four kinds of retrovirus protease inhibitors (RPI-856 A, B, C and D) were isolated as white powder from the culture filtrate of a soil isolate, Streptomyces sp. AL-322 by column chromatography using Diaion HP-20, Sephadex LH-20, ODS reversed phase HPLC and SP-2SW ion exchange HPLC. The structures of these inhibitors were elucidated by physico-chemical properties, chemical reactions and spectral analyses, as valyl-ADPAA-leucyl-AOPBA-valyl-valyl-aspartic acid (RPI-856 A and B) and valyl-ADPAA-leucyl-AOPBA-valyl-valine (RPI-856 C and D) [ADPAA = 2-amino-2-(3,5-dihydroxyphenyl)acetic acid, AOPBA = 3-amino-2-oxo-4-phenylbutyric acid]. RPI-856 A and B, and RPI-856 C and D were both determined to be diasteromers each other on the asymmetric carbon in AOPBA. These four inhibitors strongly inhibited in vitro HIV-1 protease and HTLV-I protease both derived from recombinant Escherichia coli with IC50 of 10(-7) approximately 10(-8) M.
从土壤分离菌株链霉菌AL-322的培养滤液中，通过使用Diaion HP-20、Sephadex LH-20、ODS反相高效液相色谱和SP-2SW离子交换高效液相色谱进行柱色谱法，分离出四种逆转录病毒蛋白酶抑制剂（RPI-856 A、B、C和D），呈白色粉末状。通过物理化学性质、化学反应和光谱分析阐明了这些抑制剂的结构，分别为缬氨酰-ADPAA-亮氨酰-AOPBA-缬氨酰-缬氨酰-天冬氨酸（RPI-856 A和B）以及缬氨酰-ADPAA-亮氨酰-AOPBA-缬氨酰-缬氨酸（RPI-856 C和D）[ADPAA = 2-氨基-2-(3,5-二羟基苯基)乙酸，AOPBA = 3-氨基-2-氧代-4-苯基丁酸]。RPI-856 A和B，以及RPI-856 C和D在AOPBA的不对称碳上均被确定为非对映异构体。这四种抑制剂对源自重组大肠杆菌的体外HIV-1蛋白酶和HTLV-I蛋白酶均有强烈抑制作用，IC50为10(-7) 至10(-8) M。
