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PubMed1972

Hydroxyproline.

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Bone Diseases↗
PubMedDate not supplied

Phosphono peptide nucleic acids with a constrained hydroxyproline-based backbone.

DNA mimics representing negatively charged analogues of peptide nucleic acids (PNAs), particularly hetero-oligomers constructed from alternating phosphono-PNA residues (pPNA) and monomers on the base of trans-4-hydroxy-L-proline (HypNA) as well as mimics composed of phosphono-HypNA monomers (pHypNA) were tested in a set of in vitro and in vivo assays, and they demonstrated a high potential for the use in nucleic acid based diagnostic, isolation of nucleic acids and antisense experiments.

Base Sequence↗
PubMed1984

Effect of calcium supplementation on urinary hydroxyproline in osteoporotic postmenopausal women.

Although calcium supplements are widely used to reduce bone resorption in osteoporosis, their beneficial effect is not conclusively established. We studied the effect of a calcium supplement (1 g/day for 8 days) in 14 postmenopausal osteoporotic women. The fasting urinary hydroxyproline/creatinine ratio decreased from 0.022 +/- 0.001 to 0.017 +/- 0.001 (p less than 0.005) indicating a significant reduction in bone resorption. Both the tubular maximum for phosphate reabsorption (1.12 +/- 0.06 to 1.34 +/- 0.07, p less than 0.005) and plasma phosphate concentration (1.04 +/- 0.04 to 1.14 +/- 0.04, p less than 0.01) increased, consistent with suppression of parathyroid hormone activity. These results support the concept that calcium supplementation is useful in the treatment of postmenopausal osteoporosis.

Aged↗
PubMed2006

Hydroxyproline-based DNA mimics provide an efficient gene silencing in vitro and in vivo.

To be effective, antisense molecules should be stable in biological fluids, non-toxic, form stable and specific duplexes with target RNAs and readily penetrate through cell membranes without non-specific effects on cell function. We report herein that negatively charged DNA mimics representing chiral analogues of peptide nucleic acids with a constrained trans-4-hydroxy-N-acetylpyrrolidine-2-phosphonate backbone (pHypNAs) meet these criteria. To demonstrate this, we compared silencing potency of these compounds with that of previously evaluated as efficient gene knockdown molecules hetero-oligomers consisting of alternating phosphono-PNA monomers and PNA-like monomers based on trans-4-hydroxy-L-proline (HypNA-pPNAs). Antisense potential of pHypNA mimics was confirmed in a cell-free translation assay with firefly luciferase as well as in a living cell assay with green fluorescent protein. In both cases, the pHypNA antisense oligomers provided a specific knockdown of a target protein production. Confocal microscopy showed that pHypNAs, when transfected into living cells, demonstrated efficient cellular uptake with distribution in the cytosol and nucleus. Also, the high potency of pHypNAs for down-regulation of Ras-like GTPase Ras-dva in Xenopus embryos was demonstrated in comparison with phosphorodiamidate morpholino oligomers. Therefore, our data suggest that pHypNAs are novel antisense agents with potential widespread in vitro and in vivo applications in basic research involving live cells and intact organisms.

Animals↗