Structural Determinants of the Unusual Helix Stability of a De Novo Engineered Vascular Endothelial Growth Factor (VEGF) Mimicking Peptide

Diana, Donatella; Ziaco, Barbara; Colombo, Giorgio; Scarabelli, Guido; Romanelli, Alessandra; Pedone, Carlo; Fattorusso, Roberto; D’Andrea, Luca Domenico

doi:10.1002/chem.200800180

Cited by 44 publications

(42 citation statements)

References 17 publications

(16 reference statements)

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“…1C). The reported bioactive secondary structure of the VEGF-mimetic sequence is α-helical (30,31). CD of the VEGF PA revealed a signal characteristic of α-helix (Fig.…”

Section: Resultsmentioning

confidence: 95%

“…In addition, a number of synthetic strategies have emerged to modulate angiogenesis through small molecules or peptides and have been developed to antagonize receptors for cancer therapies or to promote angiogenesis by signaling through these receptors (28,29). Currently, only one synthetic oligopeptide has been demonstrated to mimic VEGF through the activation of its receptors (30,31). This peptide was designed based on the native α-helical receptor-binding domain of VEGF and was shown to mimic native VEGF through activation of VEGF receptors.…”

mentioning

confidence: 99%

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Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair

Webber

Tongers

Newcomb

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

298

268

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There is great demand for the development of novel therapies for ischemic cardiovascular disease, a leading cause of morbidity and mortality worldwide. We report here on the development of a completely synthetic cell-free therapy based on peptide amphiphile nanostructures designed to mimic the activity of VEGF, one of the most potent angiogenic signaling proteins. Following self-assembly of peptide amphiphiles, nanoscale filaments form that display on their surfaces a VEGF-mimetic peptide at high density. The VEGF-mimetic filaments were found to induce phosphorylation of VEGF receptors and promote proangiogenic behavior in endothelial cells, indicated by an enhancement in proliferation, survival, and migration in vitro. In a chicken embryo assay, these nanostructures elicited an angiogenic response in the host vasculature. When evaluated in a mouse hind-limb ischemia model, the nanofibers increased tissue perfusion, functional recovery, limb salvage, and treadmill endurance compared to controls, which included the VEGF-mimetic peptide alone. Immunohistological evidence also demonstrated an increase in the density of microcirculation in the ischemic hind limb, suggesting the mechanism of efficacy of this promising potential therapy is linked to the enhanced microcirculatory angiogenesis that results from treatment with these polyvalent VEGF-mimetic nanofibers.

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“…1C). The reported bioactive secondary structure of the VEGF-mimetic sequence is α-helical (30,31). CD of the VEGF PA revealed a signal characteristic of α-helix (Fig.…”

Section: Resultsmentioning

confidence: 95%

mentioning

confidence: 99%

Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair

Webber

Tongers

Newcomb

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

298

268

View full text Add to dashboard Cite

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“…Initially, we focused on the VEGF helix 17-25 (29). The designed 15-mer peptide assumes in water a well defined helical conformation and presents a remarkable thermal stability (30,31). It binds and activates VEGF receptors and shows VEGF-like activity in vitro (29) and in vivo (32,33).…”

Section: Discussionmentioning

confidence: 99%

β-Hairpin Peptide That Targets Vascular Endothelial Growth Factor (VEGF) Receptors

Diana

Basile

Rosa

et al. 2011

Journal of Biological Chemistry

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VEGF receptors have been the target of intense research aimed to develop molecules able to inhibit or stimulate angiogenesis. Based on the x-ray structure of the complex placental growth factor-VEGF receptor 1 D2 , we designed a VEGF receptor-binding peptide reproducing the placental growth factor ␤-hairpin region Gln 87 -Val 100 that is involved in receptor recognition. A conformational analysis showed that the designed peptide adopts the expected fold in pure water. Moreover, a combination of NMR interaction analysis and cell binding studies were used to demonstrate that the peptide targets VEGF receptors. The VEGF receptor 1 D2 -interacting residues were characterized at the molecular level, and they correspond to the residues recognizing the placental growth factor sequence Gln -Val 100. Finally, the peptide biological activity was characterized in vitro and in vivo, and it showed a VEGF-like behavior. Indeed, the peptide activated VEGF-dependent intracellular pathways, induced endothelial cell proliferation and rescue from apoptosis, and promoted angiogenesis in vivo. This compound is one of the few peptides known with proangiogenic activity, which makes it a candidate for the development of a novel peptide-based drug for medical applications in therapeutic angiogenesis.

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“…107 Similar to the peptide sequence in native VEGF, 104,108 the sequence folded into an alpha-helical conformation. It was found that the VEGF-mimetic peptide was able to bind the VEGF receptors of HUVECs and thereby improved migration, proliferation and survival of the cells.…”

Section: Cell Signaling By Supramolecular Materialsmentioning

confidence: 99%

25th Anniversary Article: Supramolecular Materials for Regenerative Medicine

2014

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In supramolecular materials, molecular building blocks are designed to interact with one another via non-covalent interactions in order to create function. This offers the opportunity to create structures similar to those found in living systems that combine order and dynamics through the reversibility of intermolecular bonds. For regenerative medicine there is a great need to develop materials that signal cells effectively, deliver or bind bioactive agents in vivo at controlled rates, have highly tunable mechanical properties, but at the same time, can biodegrade safely and rapidly after fulfilling their function. These requirements make supramolecular materials a great platform to develop regenerative therapies. This review illustrates the emerging science of these materials and their use in a number of applications for regenerative medicine.

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Structural Determinants of the Unusual Helix Stability of a De Novo Engineered Vascular Endothelial Growth Factor (VEGF) Mimicking Peptide

Cited by 44 publications

References 17 publications

Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair

Supramolecular nanostructures that mimic VEGF as a strategy for ischemic tissue repair

β-Hairpin Peptide That Targets Vascular Endothelial Growth Factor (VEGF) Receptors

25th Anniversary Article: Supramolecular Materials for Regenerative Medicine

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