Abstract: Improvements in methods of treating cancer with weakly basic anti-cancer compounds are provided. In one aspect, the invention provides an improvement in a method of treating cancer cells whose extracellular environment contains 1–8 mM urea, by exposing the cells to a weakly basic anti-cancer compound which is effective in inhibiting the growth of the cells. The improvement includes (a) exposing the cells to a urease enzyme composition and, (b) by step (a), reducing the amount of anti-cancer compound required to produce a given extent of inhibition in the growth of the cells when the cells are exposed to the anti-cancer agent. Methods of potentiating the specific therapeutic activity of a weakly basic anti-cancer compound in the treatment of a given mammalian cancer which is responsive to the compound are provided as are pharmaceutical compositions for use in intravenous administration to a subject are also provided.

Abstract: A pharmaceutical composition and method for use in inhibiting growth of cancer cells in a mammalian subject are disclosed. The composition includes a urease enzyme, and associated therewith, a chemical entity effective to enhance the delivery of the enzyme to cancer cells, when the composition is administered to the subject. Also disclosed are a method of enhancing the effectiveness of weakly basic anti-tumor compounds, a method assessing the presence, size or condition a solid tumor in a subject, and a gene therapy composition for treating a cancer in a subject.

Abstract: Improvements in methods of treating cancer with weakly basic anti-cancer compounds are provided. In one aspect, the invention provides an improvement in a method of treating cancer cells whose extracellular environment contains 1-8 mM urea, by exposing the cells to a weakly basic anti-cancer compound which is effective in inhibiting the growth of the cells. The improvement includes (a) exposing the cells to a urease enzyme composition and, (b) by step (a), reducing the amount of anti-cancer compound required to produce a given extent of inhibition in the growth of the cells when the cells are exposed to the anti-cancer agent. Methods of potentiating the specific therapeutic activity of a weakly basic anti-cancer compound in the treatment of a given mammalian cancer which is responsive to the compound are provided as are pharmaceutical compositions for use in intravenous administration to a subject are also provided.

Abstract: A diagnostic method and device for use in detecting or quantitating an analyte present in a liquid sample. The method includes reacting an analyte-containing sample with reagents capable of generating a first coil-forming peptide in solution form. This peptide is then contacted with a biosensor whose detection surface has surface-bound molecules of a second, oppositely charged coil-forming peptide, under conditions effective to form a stable &agr;-helical coiled-coil heterodimer on the detection surface. The formation of the coiled-coil heterodimer produces a measurable change in biosensor signal, which is measured to detect the presence of or quantitate the amount of analyte in a sample. Also disclosed is a biosensor device for carrying out the reaction.

Abstract: A pharmaceutical composition and method for use in inhibiting growth of cancer cells in a mammalian subject are disclosed. The composition includes a urease enzyme, and associated therewith, a chemical entity effective to enhance the delivery of the enzyme to cancer cells, when the composition is administered to the subject. Also disclosed are a method of enhancing the effectiveness of weakly basic anti-tumor compounds, a method assessing the presence, size or condition a solid tumor in a subject, and a gene therapy composition for treating a cancer in a subject.

Abstract: A protein interaction method and composition are described. The method and composition are useful for a number of purposes including: reconstituting multisubunit protein complexes, identifying known binding subunits, determining the kinetics and order of self assembly of a multisubunit protein complex, and drug screening. The method involves contacting a conjugate with a solid surface having an immobilized first coil-forming peptide characterized by a selected charge and an ability to interact with a second, oppositely charged coil-forming peptide to form a stable &agr;-helical coiled-coil heterodimer, where the conjugate comprises (a) the second, oppositely charged coil-forming peptide, and (b) a first subunit polypeptide which is one of a plurality of subunit polypeptides in a multisubunit complex. By said contacting the conjugate is bound to the solid surface. Other subunits of the complex are added under conditions effective to promote self-assembly of the subunit complex on the solid surface.

Abstract: A method for presenting a target protein or an array of target proteins for analysis is disclosed. The method includes the steps of forming a coding sequence; placing the coding sequence and protein-synthesis components capable of expressing the target protein under selected protein-synthesis conditions in a well on a substrate, the well having a surface which has been functionalized with the second coil-forming peptide; expressing said coding sequence under such conditions, wherein the target protein so synthesized binds to the well through coil-coil heterodimer formation, and is thus presented for analysis in the well in captured form; and washing said well to remove unbound components.

Abstract: A diagnostic card device for use in detecting or quantitating an analyte present in a liquid sample, comprising a card substrate having a sample introduction region, a biosensor, and a sample-flow pathway communicating between the sample-introduction region and the biosensor, circuitry for generating an analyte-dependent electrical signal from the biosensor; and a signal-responsive element for recording such signal. In one embodiment, the biosensor includes a detection surface with surface-bound molecules of a first charged, coil-forming peptide capable of interacting with a second, oppositely charged coil-forming peptide to form a stable &agr;-helical coiled-coil heterodimer, where the binding of the second peptide to the first peptide, to form such heterodimer, is effective to measurably alter a signal generated by the biosensor. The sample-flow pathway contains diffusibly bound conjugate of the second coil-forming peptide and the analyte (or an analyte analog) and immobilized analyte-binding agent.