306 - RGD

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. ° ... 

RGD analogs have been shown to inhibit the attachment of osteoclasts to bone matrix and to reduce bone resotptive activity in vitro. The cell surface integrin, av 33, appears to play a role in this process. RGD analogs may rq resent a new approach to modulating osteoclast-mediated bone resorption and may be useful in the treatment of osteoporosis [9]. 

Horton MA, Taylor ML, Arnett TR et al (1991) Arg-Gly-Asp (RGD) peptides and the anti-vitronectin receptor antibody 23C6 inhibit dentine resorption and cell spreading by osteoclasts. Exp Cell Res 195 368-375... 

Repeated addition of MDC to Q11 did occur, but the dominant product was Q11 with a single MDC. The fraction of Qll with higher numbers of attached MDC decreased for increasing MDC number. Separately, a lysine peptide that contained the bioactive RGD [73] sequence ( -dansyl-GLKGGRGDS-Am) was successfully TGase crosslinked with self-assembled Qll five distinct Qll-dansyl RGD were detected by mass spectrometry. 

YAVTGRDGSPASSKPIA((VPGIG)2VPGKG(VPGIG)2)4VP)3-LE Scrambled RGD Elastin-Iike domain... 

Fig. 15 Amino acid sequences of artificial extracellular matrix (aECM) proteins. Each protein contains a TV tag, a histidine tag, a cleavage site, and elastin-like domains with lysine residues for crosslinking. The RGD cell-binding domain is found in aECM 1, whereas aECM 3 contains the CS5 cell-binding domain. aECM 2 and aECM 4 are the negative controls with scrambled binding domains for aECM 1 and aECM 3, respectively. Reprinted from [121] with permission from American Chemical Society, copyright 2004...

In another study, the original repetitive Cio, (AGAGAGPEG)io, center was reconstructed into nine repeats of AGAGAGPEG with three distributed repeats of the RGD sequence. The new triblock protein, composed of acidic and basic terminal domains in addition to the reconstructed central block, has been shown to support adhesion, spreading, and polarization of human fibroblast cells [82]. Triblock polypeptides that facilitate antibody binding have also been reported [83]. 

Ruoslahti E, Pierschbacher MD (1987) New perspectives in cell-adhesion - RGD and integrins. Science 238 491M97... 

Mitra A, Mulholland J, Nan A et al (2005) Targeting tumor angiogenic vasculature using polymer-RGD conjugates. J Control Release 102 191-201... 

Burdick JA, Anseth KS (2002) Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. Biomaterials 23 4315-4323... 

VandeVondele S, Voros J, Hubbell JA (2003) Rgd-grafted poly-l-lysine-graft- (polyethylene glycol) copolymers block non-specific protein adsorption while promoting cell adhesion. Biotechnol Bioeng 82 784—790... 

Chun C, Lim HJ, Hong KY et al (2009) The use of injectable, thermosensitive poly (organophosphazene)-RGD conjugates for the enhancement of mesenchymal stem cell osteogenic differentiation. Biomaterials 30 6295-6308... 

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

H. N-methylated cyclic RGD peptides as highly active and selective (X,P3 integrin antagonists. J. Med. Chem. 1999, 42, 3033-3040. 

RGD Arginine-glycine-asparagine rh- Recombinant human - (prefix usually referring to peptides)... 

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 neoangiogenic tumor vasculature overexpresses certain integrins and other surface markers, which can also be used for targeting of polyplexes. The RGD peptide motif has been successfully applied for integrin-targeted pDNA [125-128] and siRNA [129, 130] delivery. In many cases, the PEG motif-containing peptide was attached to the polycation via a PEG spacer. For RGD-PEG-PEI/pDNA polyplexes, an optimum grafting with RGD-PEG was required because transfection... 

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