Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist

Escalated Aggression after Alcohol Drinking in Male Mice: Dorsal Raphé and Prefrontal Cortex Serotonin and 5-HT1B Receptors

“…It is significant that the expression of Alc-heightened aggression was insensitive to intra-raphé infusion of either of these agonists in light of the recent report by Bannai et al (2007) showing a significant reduction in schedule-heightened aggression by intra-raphé infusion of a different 5-HT 1B agonist, CP-93,129. Both CP-94,253 and CP-93,129 have a high affinity for the 5-HT 1B receptor but differ in their relative affinities for the 5-HT 1B receptor vs the 5-HT 1A receptor (K i for 5-HT 1A : 5-HT 1B ¼ 44.5 and 27.27 nM, respectively; Koe et al, 1992a, b;Perez et al, 1998;Pineyro and Blier, 1999). The greater relative affinity of CP-93,129 for the 5-HT 1A receptor may account for why this ligand was able to effectively reduce heightened aggressive behavior in contrast to CP-94,253 when infused into a region abundant with 5-HT 1A receptors.…”

A New Way to Silicone‐Based Peptide Polymers

“…Enhancement of the biological effects was reported using dimeric analogues of numerous hormones (i.e. enkephalins, [25] neurokinins, [26] bradykinin, [27] serotonin [28] ), of pharmaceutical drugs [29] and was also reported to inhibit protein-protein interaction. [30] The reported strategies mostly rely on the linking of a spacer arm on the solid support and the simultaneous synthesis of the two "arms" from the C to the N-terminus, on the coupling of protected peptides bearing a single free reactive function on the spacer or on chemoselective ligation.…”

“…Advantageously, no protection was required on the side chains, and the chlorodimethylsilane function could be introduced easily at the N-terminus (or at any point of the sequence through a lysine side chain). 29 Si NMR spectroscopy demonstrated that all silicon atoms are engaged in siloxane bonds. On the contrary, LC-MS analyses showed the presence of monomers and dimers because of hydrolysis of dimers in the acidic eluents.…”

“…As a consequence of the insolubility these polymers only hypotheses can be drawn, however this low T g may be attributed to the presence of cyclic species containing only SiOSi bonds. Soluble polymers were analyzed by steric exclusion chromatography (SEC; Figure 3) and 29 Si NMR spectroscopy. SEC chromatograms clearly showed that type B linear polymers polymers had significantly higher molecular weight than their type C counterparts.…”

“…In opposition to B linear polymers, the polymerization degree of type C comb polymers seemed strongly impacted by the peptide sequence probably because of steric hindrance of pendant chains upon polymerization. 29 Si NMR spectra (Supporting Information) of polymers B4, B5, C1, C4, and C5, which were soluble in DMSO were recorded. Integration of the signal at 7.9 ppm assigned to M 1 substructures, which corresponded to silicon atoms involved in SiOSi bonds, as well as integration of the signal at 11.5 ppm (M 0 substructures) related to silanol end groups (SiOH), were used to calculate the SiOSi/SiOH ratio, which corresponded to half of the polydispersity index estimated by NMR spectroscopy (DP NMR ).…”