Tachykinins structure

Almeida TA, Rojo J, Nieto PM et al (2004) Tachykinin and tachykinin receptors structure activity relationships. Curr MedChem 11 2045-2081... 

Satake H, Kawada T (2006) Overview of the primary structure, tissue distribution, and function of tachykinins and their receptors. Curr Drug Targets 7 963-974... 

Tachykinins are among the most abundant neuropeptides in the central nervous system. Limbic structures, which are important in the control of emotional behaviors, in particular contain tachykinins and neurokinin receptor sites in high density (Honkaniemi et al. 1992 Hurd et al. 1999 Ribeiro-da-... 

A similar strategy has been used to optimize a number of peptide-based compounds with therapeutic potential, including tachykinins, enkephalins, and protease inhibitors. HIV protease is essential for producing mature, infectious virus, and two protease molecules are carried in each mature virion (Figure 4.7). With inhibitors developed specifically for HIV protease, but not human protease, one hopes to halt virus replication. Peptides with HIV protease inhibitor activity have been further refined by means of computer- and structure-based design strategies, leading to the development of new molecular entities that are stable to proteases and compact so that they can be administered orally (Table 4.6). Some protease inhibitors (e.g., ritonavir and... 

Substance P belongs to the tachykinin family of peptides, which share the common carboxyl terminal sequence Phe-X-Gly-Leu-Met. Other members of this family are neurokinin A and neurokinin B. Substance P is an undecapeptide, while neurokinins A and B are decapeptides. They have the following structures ... 

Fig. 13. Primary structures in the family of tachykinins Pyr = pyroglutamic acid...

Donnelly, D., Maudsley, S., Gent, J. P., Moser, R. N., Hurrell, C. R., Findlay, J. B. C. Conserved polar residues in the transmembrane domain of the human tachykinin NK2 receptor Functional roles and structural implications. Biochem. J., 1999, 339, 55-61. 

Horwell, D.C., Howson, W., Higginbottom, M., Naylor, D., Ratcliffe, G.S. and Williams, S. (1995). Quantitative Structure-Activity Relationships (QSARs) of N-Terminus Fragments of NKl Tachykinin Antagonists A Comparison of Classical QSARs and Three-Dimensional QSARs from Similarity Matrices. J.Med.Chem.,38, 4454-4462. 

All structures were selected from the Ensemble database. In addition to approved therapeutic agents these particularly include a set of lead compounds entered in advanced clinical/preclinical trials (a total of 16,540 compounds). Structures were extracted according to the assigned activity class, where the class indicates a common target-specific group such as GPCRs, kinases and proteases, nuclear receptors, and ion channels as well as more than 150 subclasses (for example, serotonin, tachykinin and dopamine receptors, tyrosine, Abl, Aurora and serine/threonine kinases, cysteine and serine proteases, etc.). Prior to the statistical experiments, the molecular structures should be filtered and normalized in order to fulfill certain criteria (see Subheading 3.5 and 4). 

Because of specific cluster structure determined by the internal activation (neuron) function originally realized in the Kohonen-based SOMs it is very difficult to obtain a fully scalable and, at the same time, adequate map with the preservation of all the distances observed among all input samples. Fortunately, using the constructed map it is quite possible to set the zoom into the GPCR area. Thus, compounds acting specifically on different GPCR subclasses including a/ p-adrenoceptors, dopamine D1-D4 receptors, tachykinin NK1/NK2, serotonin and chemokine receptors can also be successfully separated within the same map (Fig. 3a-i). 

A. Chollet, Probing the structure and function of the tachykinin neurokinin-2 receptor through biosynthetic incorporation of fluorescent amino acids at specific sites,/. Biol. Chem. 1996, 271, 19991-19998. 

Eledoisin, peptide amide from the salivary glands of the cephalopod (Eledone moschata and E. aldrovandi) belonging to the tachykinin family. Its biological activities in vitro are similar to those of substance P. The solution structure has been studied by two-dimensional NMR spectroscopy and distance geometry calculations [V. Erspamer,... 

Kassinin, DVPKSDQFVG LMa, a 12-peptide amide belonging to the tachykinin family. Kassinin was isolated from methanol extracts of the skin of the African frog Kassina senegalensis in 1977. It causes contraction of smooth muscle preparations at an activity of only 0.5% compared with substance P. The aqueous- and lipid-induced structure of kassinin has been studied using 2D H-NMR [A. Anastasi et al., Experientia 1977, 33, 857 R. C. Grace etal.,J. Biomol. Struct. Dyn. 2001, 18, 611]. 

Scyliorhinin I (Scy I), H-Ala-Lys-Phe-Asp-Lys-Phe-Tyr-Gly-Leu-Met -NH2, a tachykinin tachykinin family) with limited structural similarity to mammalian substance P. Scy I is a 10-peptide amide isolated from the intestine of the dogfish Scyliorhinus caniculus, with tachykinin-like activity. Scy I is the only known tachykinin that shows high affinity for both NK-1 and NK-2 binding sites, and low affinity for NK-3 binding sites [J. M. Cordon et al.. 

L-Diphenylalanine is a constrained amino acid which has been used for structure-activity studies on the tachykinin receptor.25.26 Despite its steric hindrance, this amino acid... 

Figure 10. The vertebrate tachykinin substance P is illustrated below with its C-terminal pentapeptide active core underlined. Above is the structure of the non-peptide substance P mimetic CP-96,345-1 (28),...

Several multi-ligand/multi-receptor systems are known in which multiple structurally related peptide hgands bind to various GPCRs that belong to a common receptor family. The neuropeptide Y family, the tachykinin system and the melanocortin system, just to mention a few, are known to exhibit important functions in the organism and therefore have been intensively investigated for years by SAR studies based on synthetically derived analogs. 

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