33507-63-0Relevant articles and documents
Tachykinin NK-1 receptor probed with constrained analogues of substance P
Sagan, Sandrine,Josien, Hubert,Karoyan, Philippe,Brunissen, Alie,Chassaing, Gerard,Lavielle, Solange
, p. 2167 - 2178 (2007/10/03)
The action of rotameric probes introduced either in position 7 or 8 in the sequence of substance P (SP) was investigated, i.e. L-tetrahydroisoquinoleic acid (Tic) L-fluorenylglycine (Flg), L-diphenylalanine (Dip), the diastereoisomers of L-1-indanylglycine (Ing) and L-benz[f]indanylglycine (Bfi), the Z- and E-isomers of dehydrophenylalanine and dehydronaphthylananine (Δ(Z)Phe, Δ(E)Phe, Δ(Z)Nal, Δ(E)Nal) and L-o,o'-dimethylphenylalanine (Dmp). The aim of this study was the topographical characterization of the binding subsites of human NK-1 receptor expressed in CHO cells, especially the S7 and 8, subsites, corresponding to residues Phe7 and Phe8 of substance P. According to the binding potencies of these substituted-SP analogues, the S7 binding subsite is smaller than the S8 subsite: the S7 subsite accepts only one aromatic nucleus, while the S8 can accommodate three coplanar nuclei altogether. These findings are compatible with the idea that the S8 binding subsite may reside in the extracellular loops of the hNK-1 receptor. NK-1 agonists bind to human NK-1 receptor and activate the production of both inositol phosphates and cyclic AMP. As already quoted for septide, [pGlu6, Pro9]]SP(6-11), discrepancies are observed between affinity (K(i)) and activity (EC50) values for IPs production. While a weak correlation between K(i) and EC50 values for IPs production could be found (r=0.70), an excellent correlation could be demonstrated between their affinities (K(i)) and their potencies (EC50) for cAMP production (r=0.97). The high potency (EC50) observed for 'septide-like' molecules on PI hydrolysis, compared to their affinity is not an artefact related to the high level of NK-1 receptors expressed on CHO cells since a good correlation was found between EC50 values obtained for PI hydrolysis and those measured for spasmogenic activity in guinea pig ileum bioassay (r=0.94).
Catalytic Transfer Hydrogenation in Synthesis of Substance P
Sivanandaiah, K. M.,Rangaraju, N. S.
, p. 787 - 792 (2007/10/02)
The utility of catalytic transfer hydrogenation (CTH) in the synthesis of longer peptides has been demonstrated by the stepwise synthesis of Substance P in the solution phase.The technique of CTH using formic acid as a hydrogen donor provides a facile method for the removal of protecting groups such as benzyloxycarbonyl and nitro in the synthesis of medium-sized peptides also.Except in the case of glutaminyl peptides where the purity and yield are affected to some extent by cyclization, the products are generally pure requiring minimum purification and the yields are good.
Synthesis and Radioiodination of Analogues of Substance P for the Building up of a Radioimmunoassay
Bienert, M.,Schmidt, H. E.,Ehrlich, A.,Forner, K.,Klauschenz, E.,et al.
, p. 97 - 100 (2007/10/02)
The substance P (SP) analogs 3>-SP, 8>-SP, 8, Nle11>-SP and 1>-SP have been synthesized by classical methods of peptide synthesis as well as by the liquid phase peptide synthesis (LPPS) to allow conjugation with protein in the Nα-position and radioiodination. 8>-SP and 1>-SP have been radioiodinated by the chloramine T- and the lactoperoxidase method.A complete S-oxidation of SP was observed, when the chloramine T procedure was used, but this modification does not disturbe the assay.The introduction of the 1>-SP-tracer led to considerable improvements of our SP-radioimmunoassay.
