Fluorescamine is a new reagent for the detection of primary amines in the picomole range. Its reaction with amines is almost instantaneous at room temperature in aqueous media. The products are highly fluorescent, whereas the reagent and its degradation products are nonfluorescent. Applications are discussed.
The central problem in cancer chemotherapy is the severe toxic side effects of anticancer drugs on healthy tissues. Invariably the side effects impose dose reduction, treatment delay, or discontinuance of therapy. To limit the adverse side effects of cancer chemotherapy on healthy organs, we proposed a drug delivery system (DDS) with specific targeting ligands for cancer cells. The proposed DDS minimizes the uptake of the drug by normal cells and enhances the influx and retention of the drug in cancer cells. This delivery system includes three main components: (i) an apoptosis-inducing agent (anticancer drug), (ii) a targeting moiety-penetration enhancer, and (iii) a carrier. We describe one of the variants of such a system, which utilizes camptothecin as an apoptosis-inducing agent and poly(ethylene glycol) as a carrier. Luteinizing hormone-releasing hormone ( adverse side effects ͉ apoptosis ͉ cancer ͉ targeted drug delivery T he efficacy of cancer chemotherapy is limited by severe adverse side effects induced by anticancer drugs (1-4). The cytotoxic effect on healthy organs can be significantly diminished by employing special drug delivery systems (DDS) targeted specifically to cancer cells (5, 6). Targeting is especially important in circumstances where a localized tumor is removed surgically, and chemotherapy is prescribed as a follow-up preventive against potential metastases.Cancer targeting is usually achieved by adding to the DDS a ligand moiety specifically directed to certain types of binding sites on cancer cells. Several different targeting moieties were examined, including sugars (7-11), lectins (12-14), receptor ligands (5, 15-18), and antibodies (19-23) and their fragments (24). Recently, we found that the receptors for luteinizing hormone-releasing hormone (LHRH) are overexpressed in breast, ovarian, and prostate cancer cells (5,15,25). LHRH receptors (LHRHRs) are not expressed detectably in most visceral organs. We have taken advantage of this differential receptor expression and used a modified LHRH peptide as a targeting moiety on DDS to enhance drug uptake by the mentioned cancer cells and reduce the relative availability of the toxic drug to normal cells. We constructed and evaluated in vitro targeted DDS, which included (i) poly(ethylene glycol) (PEG) polymer as a carrier; (ii) camptothecin (CPT) as an anticancer drug; and (iii) modified LHRH peptide as a targeting moiety (5,15). In vitro evaluations confirmed the high anticancer activity of such conjugates against human ovarian, breast, and prostate cancer cells (15). Further, it was demonstrated that the cytotoxicity of the LHRH-targeted conjugates in human cancer cells was competitively inhibited by free LHRH peptide (25). The present investigations were aimed at evaluating the antitumor activity and apoptosis-induction capacity of the conjugates in experiments on mice bearing xenografts of human ovarian carcinoma. Tumor and organ distribution profiles of the targeted and nontargeted conjugates were also determined in these mice for cau...
Primary amino a c i d s react w i t h 2 -p h t h a l d i a l d e h y d e i n t h e p r es e n c e of mercaptans t o form i n t e n s e l y f l u o r e s c e n t d e r i v a t i v e s . By t h e u s e of reverse-phase high-performance l i q u i d chromatography, a m i x t u r e c o n t a i n i n g 26 of t h e s e d e r i v a t i v e s w a s e f f i c i e n t l y r e s o l v e d w i t h an a n a l y s i s t i m e of l e s s t h a n 35 minutes. The q u a n t i t a t i o n of t h e i n d i v i d u a l amino a c i d s w a s r e p r o d u c i b l e w i t h a n a v e r a g e r e l ative d e v i a t i o n of i: 1.4% and had a d e t e c t i o n l i m i t of a p p r o x i m a t e l y 50 femtomoles. Improvements i n t h e s t a b i l i t y and f l u o r e s c e n c e response o f l y s i n e and h y d r o x y l y s i n e were o b t a i n e d by t h e i n c o r p o r at i o n of sodium dodecyl s u l f a t e i n t h e d e r i v a t i z i n g medium. Applic a t i o n s of t h e chromatography system i n v o l v i n g t h e amino a c i d a n a l y s i s of p e p t i d e s a f t e r e i t h e r a c i d o r enzymatic h y d r o l y s i s a r e p r e s e n t e d . Methods f o r t h e sequence a n a l y s i s of picomole q u a n t it i e s o f p e p t i d e s by t i m e c o u r s e h y d r o l y s i s w i t h e x o p e p t i d a s e s were a l s o developed, which employed t h e above s e p a r a t i o n procedure f o r t h e i d e n t i f i c a t i o n and q u a n t i f i c a t i o n o f t h e r e l e a s e d amino a c i d s .
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