Arginine-glycine-aspartic acid

Liu et al. (2007) discovered that polyethylene glycol (PEG)ylated SWNTs are stable in vivo and demonstrate long blood circulation times and low uptake by the reticuloendothelial system. This group linked PEGylated SWNTs to an arginine-glycine-aspartic acid peptide, which was able to effectively target tumors in mice. 

Hart SL, Collins L, Gustafsson K, et al. Integrin-mediated transfection with peptides containing arginine-glycine-aspartic acid domains. Gene Ther 1997 4(11) 1225-1230. 

As a sidebar, it should be noted that there is a domain on the fibronectin molecule which binds to the simple peptide RGD (arginine-glycine-aspartic acid) and this has been explored as a means of interfering with the tumor adhesion process using longer, more stable, polypeptide sequences and other analogues or derivatives (Humphries et al. 1987). 

On such modified surfaces, some of the attached proteins are recognized by cytoskeletally associated receptors in the cell membrane. So, in the end, the extracellular substrate is mechanically connected with the intracellular cytoskele-ton, which may secrete its own adhesion proteins. Integrins, as an important class of cell receptors [63], bind to small domains on their adhesion proteins, e.g., the oligopeptide sequence arginine-glycine-aspartic acid (RGD) that is common in fibronectin [64],... 

RGD arginine-glycine-aspartic acid peptide sequence... 

Fig. 2. Schematic representation (not to scale) of the amino acid sequence of a Type I collagen. A Type I collagen consists of two identical of cd(I) and one unique a2(I) chains whose combination produces a triple helical structure 300 nm long and 0.5 nm thick, with a periodicity of 67 nm. Arginine-glycine-aspartic acid adhesive peptides ( ) start at peptide sequence 1083 in the cd(I) chain as well as at 772, 822, and 1005 in the a2(l) chain. (The schematic was redrawn using information obtained from the following references Ayad et al, 1994 Mathews and van Holde, 1990 and Darnell et al, 1990.)...

Bone sialoprotein, osteopontin, and osteocalcin are synthesized and deposited as the mineralization process begins and mineral nodules form (Stein and Lian, 1993). Bone sialoprotein contains the cell-adhesive arginine-glycine-aspartic acid peptide sequence and may thus mediate osteoblast adhesion on the extracellular matrix (Gehron-Robey, 1989). Osteocalcin, a calcium-binding protein, interacts with hydroxyapatite and is thought to mediate coupling of bone resorption (by osteoclasts) and bone formation (by osteoblasts and/or osteocytes) (Stein and Lian, 1993). 

Fig. 8. Schematic representation of protein-mediated cell adhesion on biomaterial surfaces. Biomaterial surface properties (such as hydrophilicity/hydrophobicity, topography, energy, and charge) affect subsequent interactions of adsorbed proteins these interactions include but are not limited to adsorbed protein type, concentration, and conformation. Changes in protein-surface interactions may alter accessibility of adhesive domains (such as the peptide sequence arginine-glycine-aspartic acid) to cells (such as osteoblasts, fibroblasts, or endothelial cells) and thus modulate cellular adhesion. (Adapted and redrawn from Schakenraad, 1996.)...

Fig. 11. Unfolding of vitronectin exposes epitopes for osteoblast adhesion on nanophase ceramics. Schematic representation (not in scale) of a possible mechanism for enhanced osteoblast adhesion on (a) nanophase, compared to (b) conventional, ceramics, which involves unfolding of the vitronectin macromolecule to expose select cell-adhesive epitopes (such as arginine-glycine-aspartic acid) for osteoblast adhesion. Increased exposure of cell-adhesive epitopes of vitronectin for enhanced osteoblast adhesion on nanophase ceramics may be due to nanometer surface topography and/or increased wettability due to the greater number of grain boundaries at the surface.

Fig. 8 Endothelialization on PEU surfaces modified by MPEO-derived SMAs. A Un-treated PEU surface (control) imaged by optical microscopy [OM] B MPEO-OH (without functional endgroups at the end of PEG spacers) as SMA imaged by scanning electronic microscopy [SEM] basic amino acid (typically lysine)-functionalized MPEO derivatives as SMA by C OM and D SEM arginine-glycin-aspartic acid tri-peptide sequence [RGD]-functionalized MPEO derivatives as SMA by E OM and F SEM [82,83]. Reproduced from [180,181]...

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