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1.  FGF1-gold nanoparticle conjugates targeting FGFR efficiently decrease cell viability upon NIR irradiation 
Fibroblast growth factor receptors (FGFRs) are overexpressed in a wide variety of tumors, such as breast, bladder, and prostate cancer, and therefore they are attractive targets for different types of anticancer therapies. In this study, we designed, constructed, and characterized FGFR-targeted gold nanoconjugates suitable for infrared-induced thermal ablation (localized heating leading to cancer cell death) based on gold nanoparticles (AuNPs). We showed that a recombinant ligand of all FGFRs, human fibroblast growth factor 1 (FGF1), can be used as an agent targeting covalently bound AuNPs to cancer cells overexpressing FGFRs. To assure thermal stability, protease resistance, and prolonged half-life of the targeting protein, we employed highly stable FGF1 variant that retains the biological activities of the wild type FGF1. Novel FGF1 variant, AuNP conjugates are specifically internalized only by the cells expressing FGFRs, and they significantly reduce their viability after irradiation with near-infrared light (down to 40% of control cell viability), whereas the proliferation potential of cells lacking FGFRs is not affected. These results demonstrate the feasibility of FGF1-coated AuNPs for targeted cancer therapy.
PMCID: PMC3514973  PMID: 23226697
FGF1-conjugates; gold nanoparticles; FGFR-targeted cancer therapy; photothermal therapy
2.  Two penta­dehydro­peptides with different configurations of the ΔPhe residues 
Comparison of the crystal structures of two penta­dehydro­peptides containing ΔPhe residues, namely (Z,Z)-N-(tert-butoxy­carbonyl)­glycyl-α,β-phenyl­alanyl­glycyl-α,β-phenyl­alanyl­glycine (or Boc0–Gly1–ΔZPhe2–Gly3–ΔZPhe4–Gly5–OH) methanol solvate, C29H33N5O8·CH4O, (I), and (E,E)-N-(tert-butoxy­carbonyl)­glycyl-α,β-phenyl­alanyl­glycyl-α,β-phenyl­alanyl­glycine (or Boc0–Gly1–ΔEPhe2–Gly3–ΔEPhe4–Gly5–OH), C29H33N5O8, (II), indicates that the ΔZPhe residue is a more effective inducer of folded structures than the ΔEPhe residue. The values of the torsion angles ϕ and ψ show the presence of two type-III′ β-turns at the ΔZPhe residues and one type-II β-turn at the ΔEPhe residue. All amino acids are linked trans to each other in both peptides. β-Turns present in the peptides are stabilized by intra­molecular 4→1 hydrogen bonds. Mol­ecules in both structures form two-dimensional hydrogen-bond networks parallel to the (100) plane.
PMCID: PMC2855584  PMID: 20203407
3.  Increased Protein Stability of FGF1 Can Compensate for Its Reduced Affinity for Heparin* 
The Journal of Biological Chemistry  2009;284(37):25388-25403.
Human FGF1 (fibroblast growth factor 1) is a powerful signaling molecule with a short half-life in vivo and a denaturation temperature close to physiological. Binding to heparin increases the stability of FGF1 and is believed to be important in the formation of FGF1·fibroblast growth factor receptor (FGFR) active complex. In order to reveal the function of heparin in FGF1·FGFR complex formation and signaling, we constructed several FGF1 variants with reduced affinity for heparin and with diverse stability. We determined their biophysical properties and biological activities as well as their ability to translocate across cellular membranes. Our study showed that increased thermodynamic stability of FGF1 nicely compensates for decreased binding of heparin in FGFR activation, induction of DNA synthesis, and cell proliferation. By stepwise introduction of stabilizing mutations into the K118E (K132E) FGF1 variant that shows reduced affinity for heparin and is inactive in stimulation of DNA synthesis, we were able to restore the full mitogenic activity of this mutant. Our results indicate that the main role of heparin in FGF-induced signaling is to protect this naturally unstable protein against heat and/or proteolytic degradation and that heparin is not essential for a direct FGF1-FGFR interaction and receptor activation.
PMCID: PMC2757240  PMID: 19574212

Results 1-3 (3)