Detail of "137339-65-2"

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Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides

Structure-function relationships in the activation of platelet thrombin receptors by receptor-derived peptides. Vassallo, Ralph R., Jr.; Kieber-Emmons, Thomas; Cichowski, Karen; Brass, Lawrence F. (Dep. Med., Univ. Pennsylvania, Philadelphia, PA 19104, USA). J. Biol. Chem., 267(9), 6081-5 (English) 1992. CODEN: JBCHA3.Several reagents with their cas registry numbers 141136-83-6 and 137339-65-2 are used here. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 13 (Mammalian Biochemistry) According to present models, thrombin activates platelets by cleaving its receptors after Arg41, creating a new N terminus which acts as a tethered ligand. In support of this mode, a peptide (SFLLRNPNDKYEPF or TRP42/55) corresponding to residues 42-55 has been shown to activate the receptor. In the present studies, the structural basis for thrombin receptor activation was examd. using fragments of this peptide, as well as variants of the peptide with selected amino acid substitutions. The results show that the features of SFLLRNPNDKYEPF required to mimic the effects of thrombin reside within the 1st 6 residues, SFLLRN. A hexapeptide comprised of these residues was ~5-fold more potent that the parent peptide in assays of platelet aggregation and, in addn., caused tyrosine phosphorylation, inhibition of cAMP formation, and an increase in cytosolic Ca2+. Omission of either the Ser residue or the Arg and Asn residues greatly diminished peptide activity, as did the substitution of Ala for Phe or Arg. Substitution of Ala for Ser or the initial Leu, on the other hand, had little adverse effect. The inactive peptides SALLRN and NPNDKYEPF had no effect on platelet activation initiated by SFLLRN, but FLLRN inhibited platelet aggregation in response to both SFLLRN and thrombin. These results suggest that within SFLLRN the Phe and Arg residues are particularly important and that Phe must be preceded by another amino acid, the identity of which is not tightly constrained. This observation and comparisons with the homologous domains of proteins whose tertiary structure is known were used to predict the conformation of the SFLLR sequence. The model which emerged suggests that the SFLLR domain may be part of an extended b structure in the intact receptor and that cleavage by thrombin causes it to contract and assume a modified helical configuration. In this predicted conformation the side chains of Phe and Arg point in the same direction, potentially into a pocket formed by the remainder of the receptor. .

Thrombin receptor and activation of thrombin receptor immunochemical analysis

Thrombin receptor and activation of thrombin receptor immunochemical analysis. Hosoda, Kenji; Nakamoto, Tadakatsu; Pponda, Hitomi; Kubota, Takaaki; Maruyama, Yukiro (Teijin Ltd, Japan). Jpn. Kokai Tokkyo Koho JP 08313524 A2 29 Nov 1996 Heisei, 5 pp. (Japanese). (Japan). CODEN: JKXXAF. CLASS: ICM: G01N033-53. APPLICATION: JP 1995-122464 22 May 1995. DOCUMENT TYPE: Patent CA Section: 9 (Biochemical Methods) Thrombin receptor and/or activation of thrombin receptor is detd. by a combination of flowmetry and immunostaining using monoclonal antibodies to TRAP (thrombin receptor agonist peptide), an exposed N-terminal fragment (14 amino acid) of activated thrombin receptor. Antibodies to thrombin receptor releasing fragment are also used for detn. 185995-64-6 and 137339-65-2 which are cas registry numbers of substances are two of reagents here. of the thrombin receptor and/or activation of the thrombin receptor. The method is useful for diagnosis of thrombotic diseases such as thrombosis. .