Detail of "141136-83-6"

Reference

Method for high-throughput screening

All Rights Reserved. Method for high-throughput screening. Deckmyn, Hans; Salles, Isabelle; Fontayne, Alexandre (European Cardiovascular Genetics Foundation, UK). PCT Int. Appl. WO 2007010240 A2 25 Jan 2007, 40pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LV, LY, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IS, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization).Several substances with their cas registry numbers 56985-40-1 and 141136-83-6 may be metioned in this study. CODEN: PIXXD2. APPLICATION: WO 2006-GB2664 18 Jul 2006. PRIORITY: GB 2005-14678 18 Jul 2005. DOCUMENT TYPE: Patent CA Section: 1 (Pharmacology) This invention relates to methods for assessing platelet activation. Such methods can be used to diagnose whether a subject has an increased risk of bleeding or thrombosis, to screen for compds. that are agonist or antagonists of platelet activation, or to screen for defective platelets. The invention provides a method for assessing platelet activation, which comprises: stimulating platelets in a platelet sample to cause activation of the platelets; capturing activated platelets from the platelet sample in preference to resting platelets; and detecting the captured activated platelets. .

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. .