Biological evaluation of RGD peptidomimetics, designed for the covalent derivatization of cell culture substrata, as potential promotors of cellular adhesion

Marchand‐Brynaert, Jacqueline; Detrait, Eric; Noiset, Olivier; Boxus, Thierry; Schneider, Yves‐Jacques; Remacle, Claude

doi:10.1016/s0142-9612(99)00072-1

Cited by 62 publications

(34 citation statements)

References 42 publications

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“…2A, these blocking antibodies abolished both the CF-induced up-regulation of HAS1 and down-regulation of HAS2. Furthermore, the ␣ v ␤ 3 -agonist RGDS (23,24) induced HAS1 and reduced HAS2 expression (Fig. 2B).…”

Section: Genementioning

confidence: 89%

Collagen Fragments Inhibit Hyaluronan Synthesis in Skin Fibroblasts in Response to Ultraviolet B (UVB)

Röck

Grandoch

Majora

et al. 2011

Journal of Biological Chemistry

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UVB irradiation causes characteristic features of skin aging including remodeling of the dermal extracellular matrix. A key feature during this process is the up-regulation of matrix metalloproteinases and cleavage of collagen. Hyaluronic acid (HA), a major component of the dermal matrix, decreases after chronic UVB exposure. However, the factors that govern the decline of HA synthesis during the course of actinic aging are largely unknown. The aim of the present study was to explore whether collagen degradation causes inhibition of HA synthesis in human skin fibroblasts. After treatment of fibroblasts with collagen fragments (CF) in vitro, resolution of the actin cytoskeleton and inhibition of HA secretion occurred because of specific down-regulation of hyaluronan synthase 2 (HAS2) expression. The ␣ v ␤ 3 -agonist, RGDS, latrunculin A, and an inhibitor of Rho-activated kinase inhibited HAS2 expression. Conversely, blocking antibodies to ␣ v ␤ 3 abolished the down-regulation of HAS2 and the cytoskeletal effects. Furthermore, inhibition of cofilin phosphorylation in response to CF was prevented by ␣ v ␤ 3 -blocking antibodies. The key role of ERK signaling was shown by reduced nuclear accumulation of phosphoERK and of ELK-1 phosphorylation in response to CF. In addition, the ERK inhibitor PD98059 reduced HAS2 expression. Also, UVB irradiation of fibroblasts caused down-regulation of HAS2, which was sensitive to matrix metalloproteinase inhibitors and to ␣ v ␤ 3 -blocking antibodies. In conclusion, these data suggest that CF activate ␣ v ␤ 3 -integrins and in turn inhibit Rho kinase (ROCK) signaling and nuclear translocation of phosphoERK, resulting in reduced HAS2 expression. Therefore, a novel mechanism is presented how proteolytic collagen cleavage may inhibit HA synthesis in dermal fibroblasts during extrinsic skin aging.

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Section: Genementioning

confidence: 89%

Collagen Fragments Inhibit Hyaluronan Synthesis in Skin Fibroblasts in Response to Ultraviolet B (UVB)

Röck

Grandoch

Majora

et al. 2011

Journal of Biological Chemistry

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“…• C; R f = 0.3 (SiO 2 , EtOAc-cyclohexane (10). Compound 9 (0.220 g, 0.56 mmol, 1 equiv) was dissolved in dry THF (10 mL) and the solution was cooled down to 0…”

Section: -(4-nitrobenzyloxycarbonylamino)dodecanoic Acid (9)mentioning

confidence: 99%

Design, synthesis and evaluation of graftable thrombin inhibitors for the preparation of blood-compatible polymer materials

et al. 2005

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Piperazinyl-amide derivatives of N-a-(3-trifluoromethyl-benzenesulfonyl)-L-arginine(1) were synthesized as graftable thrombin inhibitors. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro, against human a-thrombin, and in blood coagulation assay. Molecular modelling (in silico analysis) and X-ray diffraction studies of thrombin-inhibitor complexes were also performed. The fixation of bioactive molecules on poly(butylene terephthalate) (PBT) and poly(ethylene terephthalate) (PET) membranes was performed by wet chemistry treatment and evaluated by XPS analysis. Surface grafting of inhibitor 1d improved the membrane hemocompatibility by reducing blood clot formation on the modified surface.

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“…In the presence of benzotriazol-1-yl-oxy-tris-(dimethylamino)phosphonium hexafluorophosphate (PyBOP) as activating agent (Et 3 N, DMF, 20°C, 2 h), 23a and 23b reacted with 4g and 4k (0.9 equiv, DMF, 40°C, 18 h) to furnish the amides 6a,b (p = 2) and 7a,b (p = 5), respectively (Table 3, entries 1-4). (2-(2-(2-Methoxy-ethoxy)-ethoxy)-ethoxy)-acetic acid (24) 66 (spacer-arm devoid of terminal amine function) was similarly coupled to 4g and 4k, giving compounds 6c,d (entries 5-6). For biological evaluation, the precursors 6-7 were fully deprotected by treatment with TFA (50% in CH 2 Cl 2 , 20°C, 2 h) to afford the RGD peptidomimetics 8-9 (Table 4, entries 9-11 and 18-20).…”

Section: Introductionmentioning

confidence: 99%

α_vβ₃ Integrin-Targeting Arg-Gly-Asp (RGD) Peptidomimetics Containing Oligoethylene Glycol (OEG) Spacers

et al. 2009

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RGD peptides are used in biomaterials science for surface modifications with a view to elicit selective cellular responses. Our objective is to replace peptides by small peptidomimetics acting similarly. We designed novel molecules targeting R v β 3 integrin and featuring spacer-arms (for surface grafting), which do not disturb the biological activity, from (L) N-(3-(trifluoromethyl)benzenesulfonyl) tyrosine used as scaffold. Various Arg-mimics were fixed on the phenol function, and the ortho position was used for the coupling of OEG spacers. All peptidomimetics were active in the nM range in a binding test toward human R v β 3 integrin (IC 50 = 0.1 to 1.7 nM) and selective versus platelet integrin R IIb β 3 . Selected compounds revealed excellent ability to inhibit bone cells adhesion on vitronectin. Modeling and docking studies were performed for comparing the most active RGD peptidomimetic to cilengitide, i.e., cyclo-[RGDfN(Me)V]-. Lastly, the adhesion of endothelial cells on a cultivation support grafted with RGD peptidomimetics was significantly improved.

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Biological evaluation of RGD peptidomimetics, designed for the covalent derivatization of cell culture substrata, as potential promotors of cellular adhesion

Cited by 62 publications

References 42 publications

Collagen Fragments Inhibit Hyaluronan Synthesis in Skin Fibroblasts in Response to Ultraviolet B (UVB)

Collagen Fragments Inhibit Hyaluronan Synthesis in Skin Fibroblasts in Response to Ultraviolet B (UVB)

Design, synthesis and evaluation of graftable thrombin inhibitors for the preparation of blood-compatible polymer materials

α_vβ₃ Integrin-Targeting Arg-Gly-Asp (RGD) Peptidomimetics Containing Oligoethylene Glycol (OEG) Spacers

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Biological evaluation of RGD peptidomimetics, designed for the covalent derivatization of cell culture substrata, as potential promotors of cellular adhesion

Cited by 62 publications

References 42 publications

Collagen Fragments Inhibit Hyaluronan Synthesis in Skin Fibroblasts in Response to Ultraviolet B (UVB)

Collagen Fragments Inhibit Hyaluronan Synthesis in Skin Fibroblasts in Response to Ultraviolet B (UVB)

Design, synthesis and evaluation of graftable thrombin inhibitors for the preparation of blood-compatible polymer materials

αvβ3 Integrin-Targeting Arg-Gly-Asp (RGD) Peptidomimetics Containing Oligoethylene Glycol (OEG) Spacers

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α_vβ₃ Integrin-Targeting Arg-Gly-Asp (RGD) Peptidomimetics Containing Oligoethylene Glycol (OEG) Spacers