Synthesis of optically active helical poly(2-methoxystyrene). Enhancement of HeLa and osteoblast cell growth on optically active helical poly(2-methoxystyrene) surfaces.

Poly(2-methoxystyrene)s (P2MS) were synthesized using n-BuLi in THF and toluene at various temperatures. At -20 degrees C and higher temperatures, toluene was an effective polymerization solvent for synthesizing poly(2-methoxystyrene). Under these conditions, polymers with good yields and reasonable molecular weight distributions were obtained. Polymers synthesized under all conditions were isotactic; the most highly isotactic polymer was obtained in toluene at -20 degrees C. The m (isotactic dyad) content of the polymers synthesized in toluene at 0 degrees C and -20 degrees C was 0.65 and 0.74, respectively. Optically active helical (+) and (-) P2MS were synthesized by asymmetric polymerization utilizing (+) or (-) [2,3-dimethoxy1,4(dimethylamino)butane] (DDB)/tolyl lithium initiating complex in toluene. Asymmetric polymerizations were also carried out at 0 degrees C to synthesize optically active polymers. The optical rotations of the polymers were found to be dynamic and reversible, strongly suggesting contribution of the chiral higher ordered structure to the overall optical rotation. Geometry optimization carried out using various force fields such as MM+, AMBER and CHARMM suggests that isotactic P2MS form low energy stable helical conformations. HeLa cells showed better growth on surfaces prepared using chiral polymers compared to the surfaces prepared with achiral polymers. Similarly, chiral P2MS surfaces were also more effective as supports for mouse and human osteoblast cells. The cell attachment and growth data demonstrate that chiral P2MS surfaces were better supports compared to achiral P2MS surfaces. Atomic force microscopy (AFM) studies on surfaces prepared using chiral poly(2-methoxystyrene) showed more discrete topography features compared to surfaces prepared with achiral polymers. Thus, the surface topography may play a role in determining polymer-cell interactions.

An extract of Morinda citrifolia interferes with the serum-induced formation of filamentous structures in Candida albicans and inhibits germination of Aspergillus nidulans.

An aqueous extract of Morinda citrifolia was shown to interfere with the serum-induced morphological conversion of Candida albicans from a cellular yeast to a filamentous form in vitro. The conversion of C. albicans from a cellular yeast to a filamentous form in vivo is associated with pathogenicity. No significant effect on growth in serum-free media was seen at the concentrations used to interfere with the morphological change. The same extract also inhibited the germination of Apergillus nidulans spores. These results demonstrate that M. citrifolia contains a water-soluble component or components that interfere with the morphological conversion of C. albicans and the germination of A. nidulans and may have potential therapeutic value with regard to candidiasis and aspergillosis.

Helical poly(3-methyl-4-vinylpyridine)/amino acid complexes: preparation, characterization, and biocompatibility.

Helical poly(3-methyl-4-vinylpyridine) (P3M4VP)/amino acid complexes have been prepared via acid-base reaction of the achiral polymer with D and L amino acids: alanine, leucine, valine, serine and phenylalanine. The circular dichroism (CD) spectra of P3M4VP/D- and L-alanine complexes in CH(3)OH/H(2)O show opposing (near mirror image) Cotton effect signals at 278.4, 274.8 and 270.8 nm, indicating the formation of enantiomeric secondary structures. The formation of the enantiomeric structures is supported by observed [alpha](D)(25) values of -3.0 and +3.0 for the P3M4VP/D-alanine and P3M4VP/L-alanine complexes, respectively. The preparation of helical P3M4VP/amino acid complexes has been carried out in CH(3)OH and H(2)O at pH 1.8 and 2.7. The intensities of the Cotton effect signals were good. For example, for the P3M4VP/L-alanine complexes in CH(3)OH/H(2)O and H(2)O (pH 1.8), the second Cotton effect signal around 275-277 nm show [theta;] values of 49 980 and 79 210 deg . cm(2) . dmol(-1), respectively. The formation of the helical secondary structure is rapid. The acid-base reaction between P3M4VP and L-alanine in CH(3)OH/H(2)O, in 10 min, show a CD spectrum with Cotton effect signals at 274 and 272 nm with [theta] values of 27,000 deg . cm(2) . dmol(-1) and -36,000 deg . cm(2) . dmol(-1), respectively. P3M4VP permits ready conformational reorientation on complexation with amino acids, but once the helical P3M4VP/amino acid complexes are formed, it is stable at room temperature. P3M4VP is not compatible with HeLa ovarian cancer cells, but the helical P3M4VP/amino acid complexes are compatible with HeLa cells. The complexes minimally interfere with the adhesion and growth of HeLa cells on complex surfaces. Helical poly(3-methyl-4-vinylpyridine)/D- and L-alanine complexes support the attachment and growth of HeLa cells. The micrographs shows HeLa cells after three days: left panel: on P3M4VP/L-alanine complex; right panel: on P3M4VP/D-alanine complex.

Separation of the filamentous and cellular yeast forms of C. albicans following serum induction.

Following serum induction of filamentous structures in Candida albicans, the budding and filamentous forms of the organism are separated and the total protein in each form is determined. The method is useful for testing potential chemotherapeutics aimed at interference with the formation of the pathogenic, filamentous form of C. albicans.

Carvone and perillaldehyde interfere with the serum-induced formation of filamentous structures in Candida albicans at substantially lower concentrations than those causing significant inhibition of growth.

Carvone and perillaldehyde were shown to inhibit the transformation of Candida albicans to a filamentous form at concentrations far lower and more biologically relevant than the concentrations necessary to inhibit growth. This morphological transformation is associated with C. albicans pathogenicity; hence these naturally occurring monoterpenes are potential lead compounds in the development of therapeutic agents against C. albicans infection.

A protein-farnesyl transferase inhibitor interferes with the serum-induced conversion of Candida albicans from a cellular yeast form to a filamentous form.

A commercially available, cell permeable, protein-farnesyl transferase inhibitor interfered with the serum-induced morphological change in Candida albicans from a cellular yeast form to a filamentous form. The inhibitor has a negligible effect on the growth of C. albicans cells in the cellular yeast form, at the levels used to interfere with the morphological change. Conversion of C. albicans from the yeast form to filamentous form is associated with pathogenicity and hence protein-farnesyl transferase inhibitors are potentially of therapeutic value against C. albicans infection.