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Ulrich Hersel

Publications and source records attributed to Ulrich Hersel.

4 recordsLinked to original sources
PubMed2005

Photoswitched cell adhesion on surfaces with RGD peptides.

Coating of surfaces by RGD peptides is well-known. Herein we describe the possibility to switch cell adhesion properties by changing the distance and orientation of the RGD peptides to the surface. A set of RGD peptides of the type cyclo(-RGDfK-) was synthesized containing the photoswitchable 4-[(4-aminophenyl)azo]benzocarbonyl central unit as spacer between the acrylamide anchor and the RGD peptide. PMMA (poly methyl methacrylate) surfaces were coated with these peptides. Control of adhesion stimulation by irradiation with 366 or 450 nm light could be achieved.

Animals↗
PubMed2004

Two-step methodology for high-yield routine radiohalogenation of peptides: (18)F-labeled RGD and octreotide analogs.

UNLABELLED: Routine application of (18)F-labeled peptides for quantitative in vivo receptor imaging of receptor-expressing tissues and quantification of receptor status using PET is limited by the lack of appropriate radiofluorination methods for routine large-scale synthesis of (18)F-labeled peptides. To satisfy this demand, a new (18)F-labeling methodology based on the chemoselective oxime formation between an unprotected aminooxy-functionalized peptide and an (18)F-labeled aldehyde or ketone was investigated and optimized with respect to peptide conjugation. METHODS: 4-[(18)F]Fluorobenzaldehyde ([(18)F]FB-CHO) was prepared from the 4-formyl-N,N,N-trimethylanilinium precursor via direct no-carrier-added (18)F-fluorination (dimethyl sulfoxide, 60 degrees C, 15 min) and purified using a cation-exchange/reversed-phase cartridge system. Radiochemical yields (RCYs) of N-(4-[(18)F]fluorobenzylidene)oxime ([(18)F]FBOA) formation with various aminooxy-modified peptides such as minigastrin, RGD, and octreotate analogs were investigated as a function of reaction time and temperature, peptide concentration, and pH. Biodistribution studies were performed with an [(18)F]FBOA-RGD dimer ((c(RGDfE)HEG)(2)-K-Dpr-[(18)F]FBOA, 60 and 120 min after injection) and a gylcosylated [(18)F]FB-Tyr(3)-octreotate (Gluc-S-Dpr([(18)F]FBOA)TOCA), 10 and 60 min after injection) using M21 and M21L human melanoma and AR42J rat pancreatic tumor-bearing nude mice, respectively. RESULTS: [(18)F]FB-CHO was obtained in a nonoptimized RCY of 50% within 30 min. At low peptide concentrations (0.5 mmol/L), optimal [(18)F]FBOA-labeling efficiencies (60%-80%) were obtained within 15 min at 60 degrees C and pH 2-3, independently of the peptide used, affording the [(18)F]FBOA-peptides in overall RCYs of up to 40% (from end of bombardment) after purification. Both (c(RGDfE)HEG)(2)-K-Dpr-[(18)F]FBOA and Gluc-S-Dpr([(18)F]FBOA)TOCA showed pharmacokinetics suitable for early (<or=60 min) high-contrast PET imaging, high tumor uptake (2.48 +/- 0.15 %ID/g [RGD] and 21.8 +/- 1.4 %ID/g [TOCA] at 60 min after injection, where %ID/g = percentage injected dose per gram), and tumor-to-organ ratios that compared well with the corresponding [(18)F]fluoropropionyl analogs [(18)F] Galacto-RGD and Gluc-Lys([(18)F]FP)TOCA, which are prepared via multistep procedures. CONCLUSION: Oxime formation between aminooxy-functionalized peptides and an (18)F-labeled aldehyde or ketone-in this case, [(18)F]FB-CHO-combines fast 1-step, high-yield synthesis of an (18)F-labeled prosthetic group stable against in vivo defluorination with rapid, 1-step chemoselective conjugation to unprotected peptides under mild conditions. Thus, it allows fast and straightforward large-scale production of (18)F-labeled peptides for clinical routine PET application. Furthermore, it opens new perspectives to peptide radiohalogenation in general, permitting labeling of the same precursor both with diagnostic ((18)F, (124)I, (120 g)I, (123)I) and therapeutic ((211)At, (131)I) radiohalogens.

Animals↗
PubMed2003

Multimeric cyclic RGD peptides as potential tools for tumor targeting: solid-phase peptide synthesis and chemoselective oxime ligation.

The alpha v beta 3 integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Targeting this receptor may provide information about the receptor status of the tumor and enable specific therapeutic planning. Solid-phase peptide synthesis of multimeric cyclo(-RGDfE-)-peptides is described, which offer the possibility of enhanced integrin targeting due to polyvalency effects. These peptides contain an aminooxy group for versatile chemoselective oxime ligation. Conjugation with para-trimethylstannylbenzaldehyde results in a precursor for radioiododestannylation, which would allow them to be used as potential tools for targeting and imaging alpha v beta 3-expressing tumor cells. The conjugates were obtained in good yield without the need of a protection strategy and under mild conditions.

Animals↗
PubMed2003

RGD modified polymers: biomaterials for stimulated cell adhesion and beyond.

Since RGD peptides (R: arginine; G: glycine; D: aspartic acid) have been found to promote cell adhesion in 1984 (Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule, Nature 309 (1984) 30), numerous materials have been RGD functionalized for academic studies or medical applications. This review gives an overview of RGD modified polymers, that have been used for cell adhesion, and provides information about technical aspects of RGD immobilization on polymers. The impacts of RGD peptide surface density, spatial arrangement as well as integrin affinity and selectivity on cell responses like adhesion and migration are discussed.

Amino Acid Sequence↗