Opportunities in somatostatin research: biological, chemical and therapeutic aspects

Solid-phase synthesis and DNA binding studies of dichloroplatinum(ii) conjugates of dicarba analogues of octreotide as new anticancer drugs

“…1) precludes any biological application as well as the determination of the binding site (two regioisomers might be produced upon the formation of the amide bond with either the N-terminus or the side-chain of Lys 9 ). To our surprise, MS analysis revealed that in all the side-products a chloride ligand 5 had been lost and that the disulfide bond was not cleaved, suggesting the formation of several adducts differing in the ligands in the sphere of coordination of the metal. On basis of these results, we focused our work on the synthesis of an octreotide analogue, replacing the disulfide linkage with a cystine isostere.…”

“…With this idea in mind, some authors have recently reported the conjugation of platinum complexes to carrier molecules such 25 as folate, peptides that target tumor vasculature or even carbon nanotubes. 4 In our case we have focused on somatostatin, a potent endocrine hormone implicated in the regulation of many physiological processes, such as secretion, cell division, 30 proliferation and apoptosis, which are modulated by five Gprotein-coupled receptors (sst [1][2][3][4][5] ) located in the cell membrane. 5 Although all receptors are expressed to some degree in different tumors, the overexpression of subtype sst 2 is by far the most important and this fact has been exploited to 35 deliver radionuclides for molecular imaging or cytotoxic agents into tumor cells.…”

“…4 In our case we have focused on somatostatin, a potent endocrine hormone implicated in the regulation of many physiological processes, such as secretion, cell division, 30 proliferation and apoptosis, which are modulated by five Gprotein-coupled receptors (sst [1][2][3][4][5] ) located in the cell membrane. 5 Although all receptors are expressed to some degree in different tumors, the overexpression of subtype sst 2 is by far the most important and this fact has been exploited to 35 deliver radionuclides for molecular imaging or cytotoxic agents into tumor cells. 6 In order to overcome the short halflife of somatostatin in vivo, hundreds of peptide and nonpeptide analogues have been synthesized, including octreotide 1, a potent metabolically-stabilized cyclooctapeptide agonist 40 that displays high affinity and specificity to sst 2 receptor subtype.…”

“…As a DNA model we chose a short synthetic oligonucleotide, 5' dCATGGCT, which contains the target GpG doublet and gives the expected intrachain Pt-N7/5'G,N7/3'G chelate upon reaction both with cisplatin and with [Pt(en)Cl 2 ]. 16 The reaction between 6 (cis 5 isomer purified as a mixture of two diastereomers) and the oligonucleotide (1:1) was carried out in H 2 O at 37ºC (Scheme 3). As shown by HPLC, three new broad peaks with higher retention time than the parent oligonucleotide were slowly generated (20% after 24 h).…”

The Neuropeptide Systems and their Potential Role in the Treatment of Mammalian Retinal Ischemia: A Developing Story

“…SRIF-14 is virtually the only form in retina [19-20]. Five SRIF subtype receptors, displaying differences in their pharmacological and functional properties, have been cloned and designated sst1 through sst5 receptors [18, 21-23]. Of interest, different SRIF analogs have been developed as multiligand compounds [24, 25].…”