Sequence of fibrinogen

Addition of the lithium enolate of ethyl acetate to sulfinimine 153 gave 154 with a diastereomeric ratio (d.r.) of 89 11.88 Separation of the diastereoisomers by flash chromatography and deprotection with TFA/EtOH afforded the P-amino ester 155 in >97% ee and 68% overall yield. (S)-Ethyl P-amino-3-pyridinepropanoate (155) is a key component of the peptidomimetic 156 for the Arg-Gly-Asp-Phe sequence of fibrinogen. 

The sequence of fibrinogen/albumin pre-adsorption influences platelet reactions in vivo. 

Med. Chem., 35, 4914 (1992). Potent Inhibitors of Platelet Aggregation Based Upon the Arg-Gly-Asp-Phe Sequence of Fibrinogen. A Proposal on the Nature of the Binding Interactions Between the Asp-Carboxylate of RGDX Mimetics and the Platelet GP Ilb/lIIa Recep-... 

Lindmark, S. G. Panzer-Knodle, N. S. Nicholson, B. B. Taite, A. K. Salyers, L. W. King, J. G. Campion, and L. P. Feigen, /. Med. Chem., 36, 1811 (1993). Potent In Vitro and In Vivo Inhibitors of Platelet Aggregation Based Upon the Arg-Gly-Asp-Phe Sequence of Fibrinogen. A Proposal on the Nature of the Binding Interactions Between the Arg-Guanidine of the RGDX Mimetics and the Platelet GP Ilb-IIIa Receptor. 

Yudelman, Canfield, R.l. Sequence of Fibrinogen Proteolysis and Platelet Release after Intra uterine Infusion of Hypertonic Saline. 

Xemilofiban 50 (Figure 11.13) and related compounds are peptido-mimetics based on the RGD (arginine-glycine-aspartic acid) sequence of fibrinogen... 

Kudryk B Robinson D., Netre C., et al. Measurement in human blood of fibrinogen/fibrin fragments containing the B beta 15-42 sequence. Thromb Res 1982 25,277-91. 

Gorodetsky R, Vexler A, Shamir M, et al. New cell attachment peptide sequences from conserved epitopes in the carboxy termini of fibrinogen. Exp Cell Res 2003 287(1) 116-129. 

The entire amino acid sequence of all polypeptide chains of human fibrinogen has been determined by the methods of protein chemistry and later deduced from the nucleotide sequences of the cDNA coding for the polypeptide chains (Doolittle, 1984 Henschen and McDonagh, 1986). There are 610, 461, and 411 amino acids in each of the common forms of the human Act, Wft, and 7 chains, respectively. The amino acid sequences of the three chains are homologous, but important differences exist, giving rise to specific functions for certain molecular domains. 

Differential scanning microcalorimetry has been used together with limited proteolysis to identify cooperative domains in fibrinogen. It was found that each terminal part of the fibrinogen molecule is made up of six cooperative domains, with three domains formed by the C-terminal part of the /3-chain and three other domains formed by the C-terminal part of the 7-chain (Medved, 1990 Medved et at, 1986, 1997 Privalov and Medved, 1982). The amino acid sequence of the oC domains suggested that each is made up of a globular and an extended portion. Microcalorimetry... 

Fibrin polymerization is initiated by the enzymatic cleavage of the fibrinopeptides, converting fibrinogen to fibrin monomer (Fig. 1). Then, several nonenzymatic reactions yield an orderly sequence of macromolec-ular assembly steps. Several other plasma proteins bind specifically to the resulting fibrin network. The clot is stabilized by covalent ligation or crosslinking of specific amino acids by a transglutaminase, Factor XHIa. 

Bacon-Baguley, T., Ogilvie, M. L., Gartner, T. K., and Walz, D. A. (1990). Thrombospondin binding to specific sequences within the A alpha- and B beta-chains of fibrinogen. J. Biol. Chem. 265, 2317-2323. 

Parry, D. A. D. (1978). Fibrinogen A preliminary analysis of the amino acid sequences of the portions of the alpha, beta and gamma-chains postulated to form the interdomainal link between globular regions of the molecule. J. Mol. Biol. 120, 545-551. 

Wolfenstein, T. C., and Mosesson, M. W. (1981). Carboxy-terminal amino acid sequence of a human fibrinogen gamma-chain variant (gamma ). Biochem. 20, 6146-6149. 

Several potent inhibitors of fibrinogen binding to gpIIb/IIIa are now known, and some have proven to be effective antithrombotic agents. These inhibitors tend either to be small cyclic peptide mimetics, in which the conformation of an RGD sequence is constrained by macrocyclization, or they are non-peptidic molecules containing functional group mimetics of the Arg and Asp side chains, held in the correct geometry for interaction with the receptor. Examples of both classes are shown in... 

TV-terminal sections of these three chains, which are close in evolutionary terms. The a and 3 chains are terminated by a short peptide sequence called a fibrinopeptide that ordinarily prevents the spontaneous polymerisation of fibrinogen. 

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