4,7,10-Trioxa-1,13-tridecanediamine

A method of removing radiolabeled monoclonal antibodies (mAbs) from blood using a device external to the body, termed extracorporeal affinity-adsorption (EAA), is being evaluated as a means of decreasing irradiation of noncancerous tissues in therapy protocols. The EAA device uses an avidin column to capture biotinylated-radiolabeled mAbs from circulated blood. In this investigation, three trifunctional reagents have been developed to minimize the potential deleterious effect on antigen binding brought about by the combination of radiolabeling and biotinylation of mAbs required in the EAA approach. The studies focused on radiolabeling with (111)In and (90)Y, so the chelates CHX-A' '-DTPA and DOTA, which form stable attachments to these radionuclides, were incorporated in the trifunctional reagents. The first trifunctional reagent prepared did not incorporate a group to block the biotin cleaving enzyme biotinidase, but the two subsequent reagents coupled aspartic acid to the biotin carboxylate for that purpose.

In this article, we describe the synthesis of a new class of oligoethylene-glycol based water-soluble biotin derivatives for labeling of peptides with limited solubility in aqueous solution. First 4,7,10-trioxa-1,13-tridecanediamine was mono-acetylated by succinic anhydride (Ttds) followed by the introduction of N-Fmoc-protecting group using Fmoc-N-hydroxysuccinimide ester. The resulting compound (Fmoc-Ttds) was used for the preparation of 4,7,10-trioxa-1,13-tridecanediamine di- and trimers on solid phase using Wang resin by carbodiimide coupling method. After attachment of Fmoc-Ttds to the solid support, the Fmoc-blocking group was removed and the Ttds-modified resin was repeatedly acylated by Fmoc-Ttds or by biotin using PyBOP/HOBt active ester reaction. Finally the product [Fmoc-(Ttds)(n) or biotinyl-(Ttds)(n) (where n = 1, 2 or 3)] was removed from the resin by trifluoroacetic acid in the presence of water. After appropriate HPLC purification and characterization (MS) biotinyl-(Ttds)(n) (where n = 1, 2 or 3) were introduced to the N-terminal of poorly soluble oligopeptides by solid phase peptide synthesis.

The development of tumor-targeting drug delivery systems, able to selectively transport cytotoxic agents into the tumor site by exploiting subtle morphological and physiological differences between healthy and malignant cells, currently stands as one of the most attractive anticancer strategies used to overcome the selectivity problems of conventional chemotherapy. Owing to frequent overexpression of folate receptors (FRs) on the surface of malignant cells, conjugation of cytotoxic agents to folic acid (FA) via suitable linkers have demonstrated to enhance selective drug delivery to the tumor site. Herein, the chemical synthesis and biological evaluation of two novel folate-conjugates bearing the anticancer agent chlorambucil (CLB) tethered to either an aminoether (4,7,10-trioxa-1,13-tridecanediamine) or a pseudo-β-dipeptide (β-Ala-ED-β-Ala) linker is reported. The two drug delivery systems have been prepared in high overall yields (54% and 34%) through straightforward and versatile synthetic routes.

Carbon dots (C-dots) are a class of novel fluorescent nanomaterials, which have drawn great attention for their potential applications in bio-nanotechnology. Multicolor C-dots have been synthesized by chemical nitric acid oxidation using the reproducible plant soot as raw material. TEM analysis reveals that the prepared C-dots have an average size of 3.1 nm. The C-dots are well dispersed in aqueous solution and are strongly fluorescent under the irradiation of ultra-violet light. X-ray photoelectron spectroscopy characterization demonstrates that the O/C atomic ratio for C-dots change to from 0.207 to 0.436 due to the chemical oxidation process. The photo bleaching experiment reveals that the C-dots show excellent photostability as compared with the conventional organic dyes, fluorescein and rhodamine B. The fluorescence intensity of the C-dots did not change significantly in the pH range of 3-10. To further enhance the fluorescence quantum yield, the C-dots were surface modified with four types of passivation ligands, 4,7,10-trioxa-1,13-tridecanediamine (TTDDA), poly-L-lysine (PLL), cysteine and chitosan and the fluorescence quantum yields of the TTDDA, PLL, cysteine and chitosan passivated C-dots were improved 1.