13650-38-9Relevant academic research and scientific papers
The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease
Rutenber, Earl E.,De Voss, James J.,Hoffman, Lucas,Stroud, Robert M.,Lee, Kwan H.,Alvarez, Juan,McPhee, Fiona,Craik, Charles,Ortiz De Montellano, Paul R.
, p. 1311 - 1320 (2007/10/03)
A pharmacophore derived from the structure of the dithiolane derivative of haloperidol bound in the active site of the HIV-1 protease (HIV-1 PR) has been used to search a three-dimensional database for new inhibitory frameworks. This search identified an FMOC-protected N-tosyl arginine as a lead candidate. A derivative in which the arginine carboxyl has been converted to an amide has been crystallized with HIV-1 PR and the structure has been determined to a resolution of 2.5 A with a final R-factor of 18.5%. The inhibitor binds in an extended conformation that results in occupancy of the S2, S1', and S3' subsites of the active site. Initial structure-activity studies indicate that: (1) the FMOC fluorenyl moiety interacts closely with active site residues and is important for binding; (2) the N(G)-tosyl group is necessary to suppress protonation of the arginine guanidinyl terminus; and (3) the arginine carboxamide function is involved in interactions with the water coordinated to the catalytic aspartyl groups. FMOC-protected arginine derivatives, which appear to be relatively specific and nontoxic, offer promise for the development of useful HIV-1 protease inhibitors.
Isolation and characterization of Nα-Benzyloxycarbonyl amino Acid Urethane Hydrolase II from Lactobacillus fermenti 36 ATCC 9338
Matsamura, Eiko,Yamamoto, Eiko,Kawano, Tatsu,Shin, Takashi,Murao, Sawao
, p. 1563 - 1572 (2007/10/02)
A novel enzyme, which was named Nα-benzloxycarbonyl amino acid urethane hydrolase II, was purified from a cell-free extract of Lactobacillus fermenti 36ATCC 9338.The enzyme catalyzed the stoichiometric hydrplysis of N-α-benzyloxycarbonyl arginine to form benzyl alcohol and arginine.The enzyme was purified 106-fold with an activity yield of 3percent.The purified enzyme was homogeneous by disc gel electrophoresis.The molecular weight of native enzyme is about 200,000 by gel filtration, and a molecular weight of 27,000 was found for the reduced and denaturated enzyme was 5.0, it was inhibited by disodium ethylenediamine tetraacetate and p-chloromercuribenzoate, and the presence of a divalent cation, i.e.Co2+, is essential for its activity.
