N-H insertion reactions of rhodium carbenoids. Part 1. Preparation of  -amino acid and  -aminophosphonic acid derivatives.

Rh(II) acetate-catalyzed decompn. of diazophenylacetates PhC(N2)CO2Me 1 and PhC(N2)CO2R* 3 [R*OH = (-)-borneol, (+)-menthol, (-)-8-phenylmenthol] in the presence of a range of N-H compds. results in an N-H insertion reaction of the intermediate carbenoids and formation of N-substituted phenylglycine derivs. PhCH(NR1R2)CO2Me 2 [R1 = R2 = Et; R1 = 4-MeOC6H4, COCH2CHMe2, CO2CH2Ph, (S)-CH(CO2Me)CH2Ph, (S)-CHMePh, R2 = H; 64-83% yields] and PhCH(NR1R2)CO2R* 4 (R1 = R2 = Et; R1 = COMe, CO2Me, R2 = H; same R*; 37-71% yields). The corresponding reactions of di-Me ?-diazobenzylphosphonate PhC(N2)P(O)(OMe)2 5 with primary amines constitute a simple route to aminophosphonates PhCH(NHR)P(O)(OMe)2 6 (R = COMe, COEt, CO2CH2Ph, CO2CMe3, 4-ClC6H4, 4-MeC6H4, 4-MeOC6H4; 13-96% yields).

Influence of Sous Vide and Water Immersion Processing on Polyacetylene Content and Instrumental Color of Parsnip (Pastinaca sativa) Disks

The effect of blanching (95 ± 3 °C) followed by sous vide (SV) processing (90 °C for 10 min) on levels of two polyacetylenes in parsnip disks immediately after processing and during chill storage was studied and compared with the effect of water immersion (WI) processing (70 °C for 2 min.). Blanching had the greatest influence on the retention of polyacetylenes in sous vide processed parsnip disks resulting in significant decreases of 24.5 and 24% of falcarinol (1) and falcarindiol (2) respectively (p < 0.05). Subsequent SV processing did not result in additional significant losses in polyacetylenes compared to blanched samples. Subsequent anaerobic storage of SV processed samples resulted in a significant decrease in 1 levels (p < 0.05) although no change in 2 levels was observed (p > 0.05). 1 levels in WI processed samples were significantly higher than in SV samples (p = 0.05). 2 was particularly susceptible to aerobic storage following WI processing with losses of up to 70% occurring after 5 days storage. 1 type polyacetylene undergoes degradation such as oxidation, dehydrogenation when thermally treated forming oxidized form of 1 type molecules, in this case falcarindione, dehydrofalcarinol, dehydrofalcarinone. Thermal processing had a significant effect on instrumental color of parsnip samples compared to minimally processed in both SV and WI processed samples resulting in parsnip disks becoming darker, yellower and browner following processing and storage.

Modelling the effect of water immersion thermal processing on polyacetylene levels and instrumental colour of carrot disks

C₁₇ polyacetylenes are a group of bioactive compounds present in carrots which have recently gained scientific attention due to their cytotoxicity against cancer cells. In common with many bioactive compounds, their levels may be influenced by thermal processes, such as boiling or water immersion. This study investigated the effect of a number of water immersion time/temperature combinations on concentrations of these compounds and attempted to model the changes. Carrot samples were thermally treated by heating in water at temperatures from 50–100 °C and holding times of 2–60 min. Following heating, levels of falcarinol (FaOH), falcarindiol (FaDOH), falcarindiol-3-acetate (FaDOAc) and Hunter colour parameters (L^*, a^*, b^*) were determined. FaOH, FaDOH, FaDOAc levels were significantly reduced at lower temperatures (50–60 °C). In contrast, samples heated at temperatures from 70–100 °C exhibited higher levels of polyacetylenes (p < 0.05) than did raw unprocessed samples. Regression modelling was used to model the effects of temperature and holding time on the levels of the variables measured. Temperature treatment and holding time were found to significantly affect the polyacetylene content of carrot disks. Predicted models were found to be significant (p < 0.05) with high coefficients of determination (R²).

FKBPL and Peptide Derivatives: Novel Biological Agents That Inhibit Angiogenesis by a CD44-Dependent Mechanism

Purpose: Antiangiogenic therapies can be an important adjunct to the management of many malignancies. Here we investigated a novel protein, FKBPL, and peptide derivative for their antiangiogenic activity and mechanism of action.

Experimental Design: Recombinant FKBPL (rFKBPL) and its peptide derivative were assessed in a range of human microvascular endothelial cell (HMEC-1) assays in vitro. Their ability to inhibit proliferation, migration, and Matrigel-dependent tubule formation was determined. They were further evaluated in an ex vivo rat model of neovascularization and in two in vivo mouse models of angiogenesis, that is, the sponge implantation and the intravital microscopy models. Antitumor efficacy was determined in two human tumor xenograft models grown in severe compromised immunodeficient (SCID) mice. Finally, the dependence of peptide on CD44 was determined using a CD44-targeted siRNA approach or in cell lines of differing CD44 status.

Results: rFKBPL inhibited endothelial cell migration, tubule formation, and microvessel formation in vitro and in vivo. The region responsible for FKBPL's antiangiogenic activity was identified, and a 24-amino acid peptide (AD-01) spanning this sequence was synthesized. It was potently antiangiogenic and inhibited growth in two human tumor xenograft models (DU145 and MDA-231) when administered systemically, either on its own or in combination with docetaxel. The antiangiogenic activity of FKBPL and AD-01 was dependent on the cell-surface receptor CD44, and signaling downstream of this receptor promoted an antimigratory phenotype.

Conclusion: FKBPL and its peptide derivative AD-01 have potent antiangiogenic activity. Thus, these agents offer the potential of an attractive new approach to antiangiogenic therapy.