A recombinant human basic fibroblast growth factor CS23 mutein (rhbFGF-CS23) obtained from Escherichia coli cells has proliferation-stimulating activity for a fetal bovine heart endothelial cell line, ATCC CRL 1395 (biological activity), and strong affinity for heparin (heparin-affinity) similarly to the natural human basic fibroblast growth factor. Plural species having different kinds of heparin-affinity were formed by acetylation of rhbFGF-CS23 with acetic anhydride. To clarify the relationship between the sites with heparin-affinity and the biologically active sites, we have investigated the acetylation sites by peptide mapping and the biological activity of the acetylated species. Consequently, the sites with heparin-affinity in rhbFGF-CS23 are found to be Lys26, Lys119, Lys125, Lys129, and Lys135, in the primary structure, and these sites with heparin-affinity except Lys26 are also clarified to be very important to retain the biological activity of the factor.
Nitric oxide (NO) has various physiological activities. In this study, diclofenac (DF) which has a high affinity for human serum albumin (HSA) was nitrosylated to a novel NO donor (NDF). The cytotoxic effects and the mechanism of NDF were investigated.
4-phenylbutyrate (PB) and structurally related compounds hold promise for treating many diseases, including cancers. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their evaluation and clinical use. This study explores cyclodextrin (CD) complexation as a strategy to address these limitations. The structural chemistry of the CD complexes of these compounds was analyzed using phase solubility, nuclear magnetic resonance (NMR) spectroscopic techniques, and molecular modeling to inform the choice of CD for such application. The study revealed that PB and its shorter-chain derivative form 1:1 αCD complexes, while the longer-chain derivatives form 1:2 (guest:host) complexes. αCD includes the alkyl chain of the shorter-chain compounds, depositing the phenyl ring around its secondary rim, whereas two αCD molecules sandwich the phenyl ring in a secondary-to-secondary rim orientation for the longer-chain derivatives. βCD includes each compound to form 1:1 complexes, with their alkyl chains bent to varying degrees within the CD cavity. γCD includes two molecules of each compound to form 2:1 complexes, with both parallel and antiparallel orientations plausible. The study found that αCD is more suitable for overcoming the pharmaceutical drawbacks of PB and its shorter-chain derivative, while βCD is better for the longer-chain derivatives.
