Arg-GLy-Asp-Ser

The hydantoin moiety has been utilized as a biostere for the peptide linkage, transforming a peptide lead into an orally available drug candidate. Therefore, an Arg-Gly-Asp-Ser tetrapeptide (18) lead structure was modified to a non-peptide RGD mimetic as an orally active fibrinogen receptor antagonist 19. ° ... 

The binding of integrins to certain ligands is mediated by a short amino acid sequence. Thus, the binding site for fibronectin is confined to a sequence of four amino acid residues, Arg-Gly-Asp-Ser (RGDS) (R7). Synthetic peptides containing the RGDS sequence prevented adhesion of cells to fibronectin (B4, R7) and also inhibited metastasis formation in animal models (B4, R7). 

The domain structure in fibronectins is made up of a few types of peptide module that are repeated numerous times. Each of the more than 50 modules is coded for by one exon in the fibronectin gene. Alternative splicing (see p. 246) of the hnRNA transcript of the fibronectin gene leads to fibronectins with different compositions. The module that causes adhesion to cells contains the characteristic amino acid sequence -Arg-Gly-Asp-Ser-. It is these residues that enable fibronectin to bind to cell-surface receptors, known as integrins. 

Brandley and Schnaar [140] immobilized a synthetic nonapeptide, Tyr- Ala-Val Thr-Gly Arg-Gly-Asp-Ser, on a polyacrylamide gel, which had been prepared by a ternary copolymerization of acrylamide, bisacrylamide and the acrylic ester of. V-hydroxysuccinimide. They reported that Balb/c 3T3 mouse fibroblast cells (in Hepes-buffered Dulbecco s modified Eagle medium) adhered readily to the peptide-derivatized surfaces, even in the absence of serum, although long-term cell growth required the presence of serum. It was noticed that reference nonapeptide. Tyr-Arg-Leu-Glu-Asp-Pro-Ala-Met-Trp, which has no RGD sequence, failed to promote cell-attachment. 

Peptidyl macromers, in which a vinyl group was introduced at the N-terminus, were synthesized by solid-phase methodology. More specifically, the peptide H-Gly-Gly-Gly-Arg-Gly-Asp-Ser-Pro-OH had acrylic acid coupled to the N-terminus. The peptidyl macromer was cleaved and deprotected by standard methods. Copolymers of styrene with these peptidyl macromers were prepared by radical copolymerization in DMF soln. Cast films were prepared from a CHC13 soln of copolymers. 

Harfenist EJ, Packham MA, Mustard IF. Effects of the cdl adhesion peptide, Arg-Gly-Asp-Ser, cm responses ofwashedplatdets from humans, rabbits and rats Blood 1988 71 132-136... 

The currently interesting motif RODS (i.e. Arg—Gly—Asp—Ser—) present in some cell-adhesion proteins that are of crucial importance in growth and other... 

Comparative sequence analysis of even well described inter-protein interactions (i.e., from X-ray structure of multi-domain or subunit proteins) has only recently been possible initial results have however shown some common features of quaternary interactions. There is hope that interactions in naturally selfassociating proteins will be similar to those that lead to irreversible interactions in refolded proteins, and that one can then use this knowledge to prevent precipitation. For example, fibrin clots can be dissolved by adding the tetra-peptide Gly-Pro-Arg-Pro, the amino acids at the N-termini of fibrinogen molecules after thrombin cleavage. A related peptide, Arg-Gly-Asp-Ser, from the carboxy- terminus of fibrinogen, inhibits platelet aggregation. ... 

Another approach, which does not make use of either free or controlled radical polymerization, was demonstrated by Parrish et al. [20]. An aliphatic polyester with pendent acetylene groups was prepared via controlled ring-opening polymerization. Polyethylene glycol and the peptide sequence Gly - Arg - Gly - Asp - Ser (GRGDS) were functionalized with an azide moiety, and subsequently clicked to the pendent acetylenes in the... 

Fig. 3 Time course of attachment and spreading when equal amounts of MDCK II cells were seeded into the quartz dish in presence of the soluble peptides Arg-Gly-Asp (RGD), Arg-Gly-Asp-Ser (RGBS), Gly-Arg-Gly-Asp-Ser (GRGDS), and Ser-Asp-Gly-Arg-Gly (SDGRG). The concentration of each peptide was 1 mM, the cell densitiy was adjusted...

Annealing temperature, poly(vinyl alcohol) hydrogel property effect, 228-241 Arg-Gly-Asp-Ser, ftinction, 221 Arg-Gly-Asp-Ser-cairying microspheres, leukocyte activation, 220-227... 

Arg-Gly-Asp-Ser-immobilized membrane cell adhesion activity, 72-74/ coupling, 72 synthesis, 68,72... 

Transformed cells (which do not adhere to substrate) lack F., and addition of F. to some lines of transformed fibroblasts induces them to adhere to the dish and spread out. The adhesion-promoting activity can be mimicked by the tetrapeptide Arg-Gly-Asp-Ser, a sequence present in the cell attachment domain of F., or by Arg-Gly-Asp-Cys. The same tetrapeptides block adhesion of cells to F.-coated surfaces, which implies that the cell has a receptor specific for this sequence. 

Fibronectin is an adhesion protein like laminin, vitronectin, and von Wille-brand factor, which are synthesized by the cells themselves to build up the ECM. The glycoprotein fibronectin with a molecular weight between 220,000 and 250,000 consists of two similar subunits, which are connected close to their C-terminus by disulfide bridges. The subunits are composed of functional domains [121]. The cell binding domain with the characteristic sequence Gly-Arg-Gly-Asp-Ser (GRGDS) is of special interest [122]. Models of the subunit of the fibronectin molecule and its cell binding domain are presented in Fig. 21. 

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