PHOTODESTRUCTION OF TUMOR CELLS BY INDUCTION OF ENDOGENOUS ACCUMULATION OF PROTOPORPHYRIN IX: ENHANCEMENT BY 1, 10-PHENANTHROLINE

Rapidly proliferating transformed mammalian cells can be photodestroyed in vitro upon inducing the accumulation of endogenous protoporphyrin IX (Proto). Proto biosynthesis and accumulation were triggered by manipulation of the porphyrin-heme biosynthetic pathway. Proto accumulation in cultured cells was induced by treatment with 1.0 mM delta-aminolevulinic acid (ALA), a naturally occurring 5-carbon amino acid, for 3.5 h. In darkness, significant Proto accumulation became evident within 3.5 h of incubation. In the light, the accumulated tetrapyrroles triggered destruction of treated cells within the first 30 min of illumination, probably via the rapid oxidation of cellular constituents by singlet oxygen. Protoporphyrin IX accumulation and specific cell lysis increased significantly by inclusion of 0.75 mM 1,10-phenanthroline (Oph), a tetrapyrrole biosynthesis modulator. Slower growing untransformed cells did not accumulate significant amounts of Proto following ALA and Oph treatment unless stimulated to proliferate with the mitogenic lectin Concanavalin A.     

Technical and economic evaluation of different reactors for methanotrophic cultures for propylene oxide production

A two-stage process for the manufacture of propylene oxide is described. The preliminary economics based on use of methanol as a regeneration factor has resulted in a production cost of $12.10/lb of propylene oxide based on propylene oxide production rate of 40 mg/g-cell/h in conventional reactor. Increasing the propylene oxide production from 40 to 500 mg/g-cell/h resulted in a cost reduction from $12.10 to 5.8/lb of propylene oxide. The granular-activated, carbon-fluidized bed reactor (GAC-FBR) absorbs the propylene oxide and when saturated is eluted with ethyl acetate, and the bed is regenerated by steam to drive off the residual solvents. The estimated manufacturing costs are approx 59% lower (from $12.10/lb in conventional reactors to $5.00/lb for GAC-FBRs) for products that are highly inhibitory such as epoxides. In the GAC-FBR reactor, enhancing the propylene oxide production rate from 120 to 1500 mg/g-cell/h has resulted in the cost reduction to $2.00/lb. Enhancing the production capacity from 1 million lb to 10 million lb/yr has further reduced the cost of production to $1.00/lb.     

Vibrational spectroscopy of adsorbed species on nickel by neutron inelastic scattering

In a test of the utility of neutron inelastic spectroscopy (NIS) for studying molecular vibrations in surface reactions, we have examined the adsorption, co-adsorption, and reaction of hydrogen and carbon monoxide on Raney nickel catalysts.     

Energy transfer at high temperatures in the cyclopropane vem system. Temperature dependence of < ΔE' >

Collisional vibrational energy transfer between cyclopropane molecules and a seasoned silica surface has been studied by the variable encounter method at temperatures from 800 to 1325 K. The average energy of a down-transition < ΔE' > upon collision with the wall decreases monotonically with increasing temperature.     

On complexity of subset interconnection designs

Given a setX and subsetsX ₁,...,X _m, we consider the problem of finding a graphG with vertex setX and the minimum number of edges such that fori=1,...,m, the subgraphG _i; induced byX _i is connected. Suppose that for any pointsx ₁,...,x X, there are at mostX _i 's containing the set {x₁,...,x }. In the paper, we show that the problem is polynomial-time solvable for ( 2, 2) and is NP-hard for (3,=1), (=l,6), and (2,3).Support in part by the NSF under grant CCR-9208913 and CCR-8920505.Part work was done while this author was visiting at DIMACS and on leave from Institute of Applied Mathematics, Chinese Academy of Sciences, Beijing.     

Influence of Side Chain Conformation on the Activity of Glycosidase Inhibitors

Substrate side chain conformation impacts reactivity during glycosylation and glycoside hydrolysis and is restricted by many glycosidases and glycosyltransferases during catalysis. We show that the side chains of gluco and manno iminosugars can be restricted to predominant conformations by strategic installation of a methyl group. Glycosidase inhibition studies reveal that iminosugars with the gauche,gauche side chain conformations are 6- to 10-fold more potent than isosteric compounds with the gauche,trans conformation; a manno-configured iminosugar with the gauche,gauche conformation is a 27-fold better inhibitor than 1-deoxymannojirimycin. The results are discussed in terms of the energetic benefits of preorganization, particularly when in synergy with favorable hydrophobic interactions. The demonstration that inhibitor side chain preorganization can favorably impact glycosidase inhibition paves the way for improved inhibitor design through conformational preorganization.