The synthesis of RGD pepties via solid phase peptide synthesis

T1 - The synthesis of alternative diketopiperazines as potential RGD mimetics

The Synthesis of RGD-functionalized Hydrogels as a …

Decorsin is a 39-residue RGD-protein crosslinked by three disulfide bridges isolated from the leech Macrobdella decora belonging to the family of GPIIb-IIIa antagonists and acting as a potent inhibitor of platelet aggregation. Here we report the solid-phase synthesis of decorsin using the Fmoc strategy. The crude polypeptide was purified by reverse-phase HPLC in its reduced form and allowed to refold in the presence of glutathione. The homogeneity of the synthetic oxidized decorsin was established by reverse-phase HPLC and capillary zone electrophoresis. The results of amino acid analysis after acid hydrolysis of the synthetic protein, NH2-terminal sequencing and mass determination (4,377 Da) by electrospray mass spectrometry were in full agreement with this theory. The correct pairing of the three disulfide bridges in synthetic decorsin was determined by a combined approach of both peptide mapping using proteolytic enzymes and analysis of the disulfide chirality by CD spectroscopy in the near-UV region. Synthetic decorsin inhibited human platelet aggregation with an IC50 of approximately 0.1 microM, a figure quite similar to that determined utilizing decorsin from natural source. In particular, the synthetic protein was 2,000-fold more potent than a model RGD-peptide (e.g., Arg-Gly-Asp-Ser) in inhibiting platelet aggregation. Thermal denaturation experiments of synthetic decorsin, monitored by CD spectroscopy, revealed its high thermal stability (Tm approximately 74 degrees C). The features of the oxidative refolding process of reduced decorsin, as well as the thermal stability of the oxidized species, were compared with those previously determined for the NH2-terminal core domain fragment 1-41 or 1-43 from hirudin. This fragment shows similarity in size, pairing of the three disulfides and three-dimensional structure with those of decorsin, even if very low sequence similarity. It is suggested that the less efficient oxidative folding and the enhanced thermal stability of decorsin in respect to those of hirudin core domain likely can be ascribed to the presence of the six Pro residues in the decorsin chain, whereas none is present in the hirudin domain. The results of this study indicate that decorsin can be obtained by solid-phase methodology in purity and quantities suitable for structural and functional studies and thus open the way to prepare by chemical methods novel decorsin derivatives containing unusual amino acids or even non-peptidic moieties.

Synthesis and biological evaluation of dimeric RGD …

Synthesis of cyclic RGD derivatives via solid ..

Synthesis of DOTA-Conjugated Multivalent Cyclic-RGD Peptide Dendrimers via 1,3-Dipolar Cycloaddition and their Biological Evaluation: Implications for Tumor Targeting and Tumor Imaging Purposes.


118. Boros E, Ferreira CL, Yapp DT, Gill RK, Price EW, Adam MJ. . RGD conjugates of the H2dedpa scaffold: synthesis, labeling and imaging with 68Ga. 2012;39:785-94

RGD-cyclam conjugate : Synthesis and potential application for positron emission ..

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19. Glaser M, Morrison M, Solbakken M, Arukwe J, Karlsen H, Wiggen U. . Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [18F]fluorinated aldehyde-containing prosthetic groups. 2008;19:951-7

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60. Thumshirn G, Hersel U, Goodman SL, Kessler H. Multimeric cyclic RGD peptides as potential tools for tumor targeting: solid-phase peptide synthesis and chemoselective oxime ligation. 2003;9:2717-25

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17. Haubner R, Kuhnast B, Mang C, Weber WA, Kessler H, Wester HJ. . [18F]Galacto-RGD: synthesis, radiolabeling, metabolic stability, and radiation dose estimates. 2004;15:61-9

Prospective of 68Ga-Radiopharmaceutical Development

64. Chin FT, Shen B, Liu S, Berganos RA, Chang E, Mittra E. . First experience with clinical-grade ([18F]FPPRGD2): an automated multi-step radiosynthesis for clinical PET studies. 2012;14:88-95

Arginylglycylaspartic acid - Wikipedia

Human cancer cells were seeded into 6-well plates containing cover slips (to enable observation under a microscope). Bacteria strains were grown and prepared as described above. The harvested bacteria were washed twice with serum-free medium, diluted in serum-free medium, and added to each well to achieve the desired multiplicity of infection (MOI, 1:100). For the competition assay, cancer cells were incubated with the synthetic RGD peptide (final concentration, 1 μM; AnyGen Inc., Gwangju, Republic of Korea) for 2 h at 37°C before addition of RGD-displaying bacteria. The incubation was performed in a humidified atmosphere of 5% CO2 at 37°C for 2 h. The culture plates were then washed three times with PBS to remove unbound bacteria. The treated cells were examined by immunofluorescence staining (see below). Each condition was tested in triplicate, and at least three separate experiments were performed.