High-dose cytarabine in upfront therapy for adult patients with acute lymphoblastic leukaemia.

In this national study, we have evaluated a new intensive chemotherapy protocol for adult patients with untreated acute lymphoblastic leukaemia (ALL). One hundred and fifty-three patients with median age 42 years received induction therapy with high-dose cytarabine (Ara-C), cyclophosphamide, daunorubicin, vincristine and betamethasone. A high complete remission (CR) rate (90%) was achieved in patients < 60 years compared with 70% in patients > 60 years (P = 0.

Crystal structure of a bacterial cocaine esterase.

Here we report the first structure of a cocaine-degrading enzyme. The bacterial esterase, cocE, hydrolyzes pharmacologically active (-)-cocaine to a non-psychoactive metabolite with a rate faster than any other reported cocaine esterase (kcat = 7.8 s-1 and KM = 640 nM).

Convergence of Catalytic Antibody and Terpene Cyclase Mechanisms: Polyene Cyclization Directed by Carbocation-π Interactions.

A tandem cationic cyclization cascade similar to a terpenoid cyclase reaction is catalyzed by antibody HA5-19A4. The 2.7-Å resolution crystal structure of the Fab-hapten complex reveals convergence with the same catalytic strategy employed by a terpenoid cyclase: both serve as templates that enforce the productive conformation of a flexible polyene substrate, and both stabilize carbocation intermediates through cation-π interactions with multiple aromatic residues in their active sites.

Catalytic Enantioselective Retro-Aldol Reactions: Kinetic Resolution of β-Hydroxyketones with Aldolase Antibodies.

High enantiomeric enrichment after 50% conversion: Racemates of aldols can be resolved by the title reaction [Eq.(1)] by use of the aldolase antibody 38C2 or 33F12; the ee values of the unconverted aldols are greater than 95% in most cases. Since the antibodies also catalyze the aldol reaction-that is, the reverse reaction-it is possible to prepare both enantiomers using the same antibody catalysts.