DNA Binding of Porphyrin Conjugates: Characteristics and Consequences

In the past few issues of Spore, we haven t been able to accommodate all your letters and photos in Mailbox. That s why we re carrying a handsome Mailbox this time and if you want even more readers letters in the next issue, grab your pens now!MailboxIn the past few issues of Spore, we haven t been able to accommodate all your letters and photos in Mailbox. That s why we re carrying a handsome Mailbox this time and if you want even more readers letters in the next issue, grab your..

Luteinizing hormone-releasing hormone antagonists

Luteinizing hormone-releasing hormone (LH-RH) plays a central role in the vertebrate reproduction by regulating gonadal activity. Based on its binding to pituitary LH-RH receptors, as well as to LH-RH receptors expressed on cancer cells, LH-RH agonists and antagonists have been developed for different therapeutic applications.Objective/method: Here we give an overview of the most relevant LH-RH antagonists and their therapeutic applications. Recently patented compounds as well as drug formulations and dosage are presented.Conclusion: LH-RH antagonists have found clinical applications in in vitro fertilization, benign prostatic hyperplasia, endometriosis and in the treatment of hormone-dependent tumors. Work in progress is focused on further development of both peptidic and orally active non-peptidic LH-RH antagonists

Dual Labeling of Biomolecules by Using Click Chemistry: A Sequential Approach

Click by click: Dual labeling of model compounds was carried out by using copper-free and copper-mediated click chemistry in a sequential manner. This method was used to introduce two labels onto biological targets or nanoparticles, thus quickly converting them into fluorescence resonance energy transfer systems

New derivatives of GnRH as potential anticancer therapeutic agents

GnRH (gonadotropin-releasing hormone), a decapeptide produced by the hypothalamus, plays an important role in the reproduction by regulating the pituitary-gonadal axis. Continuous high doses of GnRH or its superactive agonists result in desensitization of the pituitary gonadotropes and a suppression of sex steroid production by the gonads (chemical castration). Based on these effects, the treatment with GnRH agonists has become a widely used hormonal therapy of the sex-steroid dependent tumors. It was also demonstrated that most tumor cells contain GnRH receptors, and the direct antiproliferative effect of GnRH analogs on cancer cells might be mediated by these receptors. Development of new GnRH derivatives is focused on the decrease of their hormonal potency resulting in higher selectivity of the antitumor activity. One of the most promising natural GnRH analogs, lamprey (l) lGnRH-III, was isolated from see lamprey. This variant of GnRH binds to GnRH receptors and inhibits proliferation of various cancer cells. However, its endocrine effect is insignificant in mammals. lGnRH-III dimers and conjugates were prepared and were shown to have increased antiproliferative effects on various cancer cells, while their hormonal activity was lower than that of the native hormone. lGnRH-III was applied as targeting moiety to deliver anticancer agents to tumor cells. Research data concerning lGnRH-III and its analogs represent a new outlook for research trends of the application of GnRH compounds in cancer chemotherapy. Studies on the effects of lGnRH-III derivatives including antiproliferative effects, cytotoxicity, hormonal actions, and enzymatic stability are reviewed in this article

Interaction of beta-amyloid(1-40) peptide with pairs of metal ions : an electrospray ion trap mass spectrometric model study

The stoichiometries and the affinity toward simple and paired metal ions of synthetic amyloid-β(1-40) peptide (Aβ1-40) were investigated by electrospray ion trap mass spectrometry (ESI-MS), circular dichroism (CD), and atomic force microscopy (AFM). The results lead to the working hypothesis that pH-dependent metal binding to Aβ1-40 may induce conformational changes, which affect the affinity toward other metals. A significant copper and zinc binding to Aβ1-40 peptide at pH 5.5 was found, whereas nickel ions commonly bind to each molecule of β-amyloid peptide. Some complexes of Aβ1-40 with more than one nickel ion were identified by ESI-MS. In addition, nickel ions proved to enhance Aβ oligomerization. On increasing pH, up to 12 ions of zinc may bind to a single Aβ molecule. Under the same pH and concentration conditions, the binding pattern of the independent copper and silver ions to Aβ1-40 was different from that of the equimolecular mixture of the two metal ions. One might assume that some conformational changes due to water loss altered the capacity of Aβ peptide to bind certain heavy metal ions. As a consequence, copper silver interaction with the binding process to Aβ1-40 became highly complex. A competition between silver and nickel ions for Aβ1-40 binding sites at high pH was also observed. New strategies were proposed to identify the characteristic signals for some important metal ion peptide complexes in the spectra recorded at high pH or high concentrations of metal ions. To explain the formation of such a large number of high metal ion Aβ complexes, we took into consideration the participation of both histidine residues and free amino groups as well as carboxylate ones in the binding process. Finally, CD and AFM studies supported the mass spectrometric data

Antibody Recognition and Conformational Flexibility of a Plaque-Specific beta-Amyloid Epitope Modulated by Non-native Peptide Flanking Regions

Here we report on the synthesis, antibody binding, and QSAR studies of a series of linear and cyclic peptides containing a β-amyloid plaque-specific epitope (Aβ(4 10); FRHDSGY). In these constructs, two or three α-l-Ala, α-d-Ala, or β-Ala residues were introduced at both N- and C-termini of the epitope as non-native flanking sequences. Cyclization of the linear Aβ(4 10) epitope peptide resulted in reduced antibody binding. However, the antibody binding could be fully compensated by insertion of alanine flanks into the corresponding cyclic peptides. These results indicate that the modification of a β-amyloid plaque-specific epitope by combination of cyclization and flanking sequences could generate highly antigenic peptides compared to the native sequence. A novel 3D QSAR method, which explicitly handles conformational flexibility, was developed for the case of such molecular libraries. This method led to the prediction of the binding conformation for the common FRHDSGY sequence