Philip G. Williams

Hepititol conformations revisited: C,O versus O,O parallel 1,3-interactions

Abstract The molecular and crystal structure of d - glycero - l - allo -heptitol has been determined. It crystallises in the orthorhombic space-group P 2 1 2 1 2 with a = 8.399(2), b = 23.484(8), c = 4.664(2) A, α = β = γ = 90°, and Z = 4. The heptitol was found to be in the 3 G − form, which has a 1,3-parallel interaction between C-2 and O-5. In solution, as determined by 1 H-n.m.r. spectroscopy, the heptitol and its hepta-acetate also assume conformations which have a C,O parallel interaction. Such an interaction has also been found to occur in several other heptitols and in hexose dialkyl acetals. Because conformers with such an interaction had been disregarded in the past, the conformations of several heptitols had been wrongly assigned.

Lipid domain in cancer cell plasma membrane shown by 1H NMR to be similar to a lipoprotein

Human blood lipoproteins have been characterised by 1H NMR methods and chemical analysis, and comparisons made with the properties of the triglyceride‐rich plasma membrane domain found in cancer cells. By means of selective and non‐selective T 1 experiments, the lipids in HDL and LDL are shown to be in diffusive exchange. In contrast, the lipids ofchylomicra and VLDL do not exhibit lipid diffusion, and therefore resemble the neutral lipids of cancer cell plasma membranes. 2D scalar correlated NMR (COSY) spectra of cancer cells or solid tumours are similar to those obtained from VLDL and LDL. The long T 2 relaxation value observed for neutral lipid methylenes in metastatic cancer cells (>00 ms) was not observed for any of the 4 lipoproteins studied. None of the lipoprotein classes gave a T 2 longer than 250 ms.

Cell surface involvement in cancer metastasis: an NMR study

NMR spectroscopy is one of the few techniques which has the sensitivity to detect subtle changes to the surface chemistry of cells. It has previously been demonstrated that high resolution 1H NMR methods can distinguish tumour cells with the capacity to metastasise and this information appears to arise from a type of proteolipid in or attached to the plasma membrane. Here we report that the 1H NMR signal, which we have used to identify metastatic cells in rat tumours, is significantly reduced in intensity after cultured cells are treated with trypsin/EDTA. The long T 2 relaxation value (⪢ 350 ms) observed in metastatic cells is absent after enzyme treatment. 2D scalar correlated NMR (COSY) spectra of these treated cells show that a cross peak normally associated with malignancy and metastatic disease is markedly reduced. These findings indicate that the plasma membrane lipid particle which generates the high resolution spectrum is directly affected by trypsin/EDTA. Alterations to the cell surface properties were also demonstrated in vivo since reduced numbers of metastases were observed in animals injected with enzyme‐treated cells. The correlation between the absence of a long T 2 relaxation value and the diminished numbers of metastases in animals suggests that the plasma membrane particle is involved in the metastatic process.

Vinblastine sensitivity of leukaemic lymphoblasts modulated by serum lipid

The high‐resolution proton magnetic resonance spectrum of leukaemic lymphoblasts is characteristic of neutral lipid in an isotropic environment. When such lymphoblasts are selected for resistance to the anticancer drug vinblastine, the intensity of this spectrum increases with increasing drug resistance. A reversal of this trend can be achieved by growing cells in delipidated serum, whereby lipid spectrum and drug resistance are diminished. However, both can be restored by subsequent regrowth in normal medium. Thus, although detectable genetic changes accompany the development of vinblastine resistance, the expression of these changes can be modulated by environmental lipid.