The interactions of gallium with various buffers and chelating agents in aqueous solution: gallium-71 and hydrogen-1 NMR studies.

The interactions of gallium (Ga) with the ligands, EDTA, NTA, phosphate, lactate, MOPS, TRIS and HEPES are investigated using both 71Ga and 1H nmr measurements. Both EDTA and NTA form strong complexes with gallium, which have a 1:1 stoichiometry. In alkaline solution the tetrahedral Ga(OD)4- competes strongly with EDTA in complex formation. In the lactate complex, there are probably three lactates per gallium present. The phosphate complexes of gallium are difficult to characterize on the basis of this investigation. The buffers, MOPS, TRIS, and HEPES, do not interact with gallium significantly. The ability of the ligands to bind gallium correlates well with their ability to inhibit gallium incorporation by L1210 leukemic cells.     

The genetic architecture of fitness in a seed beetle: assessing the potential for indirect genetic benefits of female choice

Background  

Quantifying the amount of standing genetic variation in fitness represents an empirical challenge. Unfortunately, the shortage of detailed studies of the genetic architecture of fitness has hampered progress in several domains of evolutionary biology. One such area is the study of sexual selection. In particular, the evolution of adaptive female choice by indirect genetic benefits relies on the presence of genetic variation for fitness. Female choice by genetic benefits fall broadly into good genes (additive) models and compatibility (non-additive) models where the strength of selection is dictated by the genetic architecture of fitness. To characterize the genetic architecture of fitness, we employed a quantitative genetic design (the diallel cross) in a population of the seed beetle Callosobruchus maculatus, which is known to exhibit post-copulatory female choice. From reciprocal crosses of inbred lines, we assayed egg production, egg-to-adult survival, and lifetime offspring production of the outbred F1 daughters (F1 productivity).     

Metabolic imaging of tumors using intrinsic and extrinsic fluorescent markers

One of the biochemical "hallmarks" of malignancy is enhanced tumor glycolysis, which is primary due to the overexpression of glucose transporters (GLUTs) and the increased activity of mitochondria-bound hexokinase in tumors. Easy methods for assessing glucose utilization in vitro and in vivo should find widespread application in biological and biomedical studies, as illustrated by the adoption of FDG PET imaging in medicine. We have recently synthesized a new NIR fluorescent pyropheophorbide conjugate of 2-deoxyglucose (2DG), Pyro-2DG, as a GLUT-targeted photosensitizer. In this study, we have evaluated the in vivo uptake of Pyro-2DG and found that Pyro-2DG selectively accumulated in two tumor models, 9L glioma in the rat and c-MYC-induced mammary tumor in the mouse, compared to surrounding normal muscle tissues at a ratio of about 10:1. By simultaneously performing redox ratio and fluorescence imaging, a high degree of correlation between the PN/(Fp+PN) redox ratio, where PN denotes reduced pyridine nucleotides (NADH) and Fp denotes oxidized flavoproteins, and the Pyro-2DG uptake was found in both murine tumor models, indicating that Pyro-2DG could serve as an extrinsic NIR fluorescent metabolic index for the tumors. The fact that only a low level of correlation was observed between the redox ratio and the uptake of Pyro-acid (the free fluorophore without the 2-deoxyglucose moiety) supports the hypothesis that Pyro-2DG is an index of the mitochondrial status (extent of PN reduction) of a tumor.     

Studies on bleomycin-DNA and bleomycin-iron interactions

The bleomycins, a group of antitumor antibiotics (Figure 1), cause the degradation of DNA by a process requiring iron(II) and dioxygen (1,2). DNA degradation appears to involve two steps: association of the drug with the nucleic acid and degradation of the DNA. As part of studies directed toward achieving an understanding of how the bleomycins degrade DNA, we have examined various properties of the drug using a variety of chemical and physico-chemical techniques, including NMR and M?ssbauer spectroscopy. We have studied both the interaction of the antibiotic with its target (DNA) as well as its association with its metal ion cofactor. This work has been performed on the intact drug and its derivatives as well as on synthetic models of the parent drug. This paper reviews and updates the recent work from this laboratory on the bleomycins.     

H nuclear magnetic resonance study of restricted internal rotation of N-6,N-6-dimethyladenine in aqueous solution.

Kinetics of internal rotation about the C(6)-N(6) bond of N-6,N-6-dimethyladenine (M2-6A) was investigated by -1H nuclear magnetic resonance line-shape analysis of the methyl resonances (220 MHz). Rates of rotation were determined for M2-6A deuterated at N(1) and for neutral M2-6A. Activation parameters for monodeuterated M2-6A at 22 degrees are Ea = 13.8kcal/mol, log A = 12.6, incrementG++=14.9 kcal/mol, incrementH++ = 13.1 kcal/mol, incrementS++ = minus 5.8 eu; for neutral M2-6A: Ea = 15.5 kcal/mol, log A = 14.9, incrementG++ = 12.6 kcal/mol, incrementH++ = 14.9 kcal/mol, incrementS++ =7.8 eu. Vertical stacking of bases interferes with internal rotation of the dimethylamino group.