RRC ID 68016
Author Casolaro M, Casolaro I, Spreafico A, Capperucci C, Frediani B, Marcolongo R, Margiotta N, Ostuni R, Mendichi R, Samperi F, Ishii T, Ito Y.
Title Novel therapeutic agents for bone resorption. Part 1. Synthesis and protonation thermodynamics of poly(amido-amine)s containing bis-phosphonate residues.
Journal Biomacromolecules
Abstract Two poly(amido-amine)s (oligoPAM and oligoNER) containing bis-phosphonate residues were obtained by a Michael-type polyaddition of pamidronate and neridronate to 1,4-bis(acryloyl)piperazine. The SEC (size-exclusion chromatography) and the MALDI-TOF (matrix assisted laser desorption ionization) analyses were consistent with the presence of oligomeric species (2-3 kDa) and with a narrow polydispersity index. The thermodynamic results (log Ks, -DeltaH(o) , and DeltaS(o) obtained at 25 degrees C in 0.15 M NaCl) of both the oligomers and the corresponding low molecular weight precursors were in line with a cluster structure formed during the protonation of the basic nitrogen in the pamidronate. The solubility of the oligoNER with a longer aliphatic chain was improved at high pHs, allowing the evaluation of their solution properties. Preliminary biological results show that both the oligomers do not negatively affect the in vitro viability, proliferation, and cellular activity of either normal animal or human osteoblasts.
Volume 7(12)
Pages 3417-27
Published 2006-12-1
DOI 10.1021/bm0607630
PMID 17154470
MeSH Bone Resorption / drug therapy* Cell Survival / drug effects Diphosphonates / chemistry* Diphosphonates / therapeutic use* Diphosphonates / toxicity Drug Design Humans Models, Molecular Pamidronate Piperazines Potentiometry Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Thermodynamics Viscosity
Human and Animal Cells MC3T3-E1(RCB1126)