RGD motif

P. Laurent, D. Tagu, D. De Carvalho, U. Nchls, R. De Beilis, R. Balestrini, G. Bauw, D. Inzc, P. Bonfante, and F. Martin, A novel class of cell wall polypeptides in PisoUthus tinctorius contain a cell-adhesion RGD motif and are up-regulated during the development of Eucalyptus globulus ectomycorrhiza. Molecular Plant Microbe Interactions (MPM ) 72 862-871 (1999). 

The conformation and orientation of adsorbed proteins has been examined with monoclonal antibodies that recognize a specific site in a protein of interest. Keselowsky et al. examined the conformation of Fn adsorbed to SAMs that carried methyl, hydroxyl, carboxyl, and amine groups [79]. They used monoclonal antibodies that recognized the central cell-binding domain of Fn near the RGD motif. Different SAM functionalities differentially modulated the binding affinities of the monoclonal antibodies (OH > COOH = NH2 > CH3). The strength of cell adhesion to these... 

A specific peptide motif linked to the chemotherapeutic molecule can enhance its efficacy, reduce their toxicity and also improve tumour cell targeting.45,51,52 Therefore, a range of glycoporphyrins 59 and 60 bearing the Arginine-Glycine-Aspartate (RGD motif) moiety were synthesised (Fig. 6). 

Other adhesion receptors that are structurally and functionally related include the receptors for fibronectin, vitronectin, platelet glycoproteins 13b and Ilia and the VLA (very-late antigen) series. All molecules involved in adhesion recognise the RGD motif and require the divalent cations Ca2+ and Mg2+ for binding. All are dimers of glycosylated proteins with relative molecular masses 95-190 kDa. There is also some sequence homology between the /J-chain (CD18) and one chain of the fibronectin receptor. 

Probably the smallest sequence known to be responsible for receptor recognition is the RGD-tripeptide, initially discovered in fibronectin [143]. However, the specificity of the interaction with different integrins, the counter receptors of RGD sequences on the cell surface, is established by the flanking sequences of the RGD motif and the conformation of the tripeptide. In other words, the presentation of the RGD sequence is important for specific recognition by individual integrins. 

Early work in the field has established the synthetic strategies and analytical tools for such class of libraries (for reviews see refs[111 112 456]). As listed in Table 13, the first generation of cyclic peptide libraries focused on biologically active sequences such as the cell adhesion RGD motif, the antileukemic heptapeptide stylostatin, or endothelin antagonists, but also on metal-binding sequence motifs and on the de novo discovery of bioactive cyclic peptides without sequence-biased motifs. Moreover, synthetic questions were addressed such as the sequence dependency of peptide cyclization reactions (see Table 13). 

All of the oncosphere antigens cloned to date contain either one of two copies of a predicted Fnlll domain. These domains are widely distributed in eukaryotic proteins and occur also in some prokaryotic proteins (Bork and Doolittle, 1992). Approximately 2% of animal proteins include Fnlll domains. Many, but not all, of these proteins are extracellular and some have roles as adhesins. The structure of this 100 amino acid domain is highly conserved and consists of two layers with three p strands in one plane and four p strands in another (Potts and Campbell, 1996). Overall, amino acid sequence identity between different Fnlll domains is low, even between Fnlll repeat domains within fibronectin itself (Plaxco et al., 1997). Nevertheless, certain residues are highly conserved and maintain the tertiary structure of the proteins (Bork and Doolittle, 1992). Other conserved motifs such as an Arg-Gly-Asp (RGD) motif within a loop of some Fnlll domains is associated with proteins having cell adhesion properties, as discussed above (Ruoslahti and Pierschbacher, 1987 D Souza et al., 1991). 

The penton for targeting to specific integrins by modification of sequences flanking the RGD motif present in the penton base [28],... 

Yousaf and coworkers used an OEG-based surface bearing hydroquinone groups for electrochemical control of cell adhesion [186]. The hydroquinone groups were electrochemically converted into quinones, to which a cyclopentadienyl-modified RGD motif was then coupled via a Diels-Alder reaction. Although the hydroquinone-bearing surface was cell-repellent, fibroblasts attached to the areas... 

Kessler and coworkers immobilized RGD peptides to a PMMA surface via a spacer incorporating an azobenzene unit [ 187]. The molecules were arranged in such a way that the RGD motifs were accessible to cells approaching the surface when the azo unit was in the E-form, and were hidden from the cells when the azo unit was in the Z-form. This enabled the reversible modulation of mouse osteoblast adhesion by irradiation with visible or UV light. However, the difference between on and off states is not very pronounced. Possibly, the accessibility of the RGD motif is not... 

Taubenberger A, Woodruff MA, Bai H F et al (2010) The effect of unlocking RGD-motifs in collagen I on pre-osteoblast adhesion and differentiation. Biomaterials 31 2827-2835... 

The RGD motif has long been known to be the principal binding motif of several integrins (77). Aumailly et al. showed that the cyclic peptide c(RGDfV), where f denotes d-phenylalanine (D-Phe), is a potent inhibitor of the integrin aubfo and determined the three-dimensional structure of the cyclic peptide from... 

Vella, F., Hernandez, J.-F., Molla, A., Block, M. R., and Arlaud, G. J. (1999) Grafting an RGD motif onto an epidermal growth factor-Uke module chemical synthesis and functional characterization of the chimeric molecule. J. Pept. Res. 54, 415-426. 

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