Solid phase synthesis in the development of magnetic resonance imaging probes

Abstract

We review the use of the solid phase synthesis methodology for the preparation of diverse and potent MRI probes.

Designed Metal-Containing Peptoid Membranes as Enzyme Mimetics for Catalytic Organophosphate Degradation

“…As shown in Figure a, six different peptoid sequences ( Pep-1 – Pep-6 ) with different numbers and chemistries of ligands were synthesized. Npy, Nqn, and Do3a were selected as ligands because they are known to coordinate transitional metal cations. ,, The Co 2+ cation was selected because of a notable enhancement in the activity of PTE when native Zn 2+ was substituted by Co 2+ . The catalytic activities of Co 2+ -containing peptoid nanomembranes made from Pep-1 to Pep-6 were tested in NEM buffer (pH 10) at room temperature.…”

Robotic synthesis of peptides containing metal-oxide-based amino acids

“…3 A variety of peptides have been fabricated in a combinatorial fashion to explore biochemical mechanisms, 10,11 develop new functional materials, 12,13 and create artificial enzymes. 14,15 To further improve bioactivity, bioavailability, and structural diversity, many unnatural inorganic residues-including metal clusters, [16][17][18] polyhedral oligomeric silsesquioxane (POSS), 19 and oligonuclear transition metal coordination complexes 18,20,21 -have been incorporated as non-canonical amino acids into peptide sequences through manual synthesis. This is important since such compounds can serve as spectroscopic or photo-affinity probes for bioassays, [18][19][20] cancer diagnoses, 16,17 and cancer-targeted therapy.…”

“…14,15 To further improve bioactivity, bioavailability, and structural diversity, many unnatural inorganic residues-including metal clusters, [16][17][18] polyhedral oligomeric silsesquioxane (POSS), 19 and oligonuclear transition metal coordination complexes 18,20,21 -have been incorporated as non-canonical amino acids into peptide sequences through manual synthesis. This is important since such compounds can serve as spectroscopic or photo-affinity probes for bioassays, [18][19][20] cancer diagnoses, 16,17 and cancer-targeted therapy. 21,22 However, there is a lack of configurability regarding charge density, redox activity, and the introduction of radical new structures and coordination systems.…”

High-Relaxivity Molecular MRI Contrast Agent to Target Gb3-Expressing Cancer Cells

“…37 Solid-phase synthesis has been advantageously used for the development of complex and specific MRI probes. 48 Success of the strategy depends on accumulation of the vector−contrastophore conjugate on the cell surface or inside the cell and therefore on its access to tumor cells, its affinity for the receptor, and the concentration of the receptor. If internalized, the intracellular trafficking pathway taken by the conjugates might have an effect because its trapping in a sub-cellular vesicle/endosome/ lysosome can quench the expected relaxation rate gain 49,50 and/or lead to the release of free toxic gadolinium.…”

“…This goal may be pursued using nanoparticles, polymers, dendrimers, liposomes, or microemulsion-conjugating multiple contrastophores to the targeting moiety − and/or taking advantage of receptor-mediated internalization to accumulate the targeted contrastophores . Solid-phase synthesis has been advantageously used for the development of complex and specific MRI probes . Success of the strategy depends on accumulation of the vector–contrastophore conjugate on the cell surface or inside the cell and therefore on its access to tumor cells, its affinity for the receptor, and the concentration of the receptor.…”