Phosphinic Dipeptide Research Articles

Synthesis, Crystal Structure and Complexing Properties of Phosphinic Analogues of Glycylglycine

The phosphinic dipeptides of the general formula H2NCH2CONHCH2P(R)(O)(OH) where R˭Me, Ph and t-Bu has been synthetized from the free phosphinic acids and N-hydroxnunimide esters of the N-protected glycine. The deprotected dipeptida were purified by combination of the column chromato graphy on strong and week cation exchange resins by elution with diluted aqueous ammonia (0.1–3%)

ChemInform Abstract: Protection of the Hydroxyphosphinyl Function of Phosphinic Dipeptides by Adamantyl. Application to the Solid‐Phase Synthesis of Phosphinic Peptides.

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Protection of the Hydroxyphosphinyl Function of Phosphinic Dipeptides by Adamantyl. Application to the Solid-Phase Synthesis of Phosphinic Peptides.

To develop solid-phase synthesis of phosphinic peptides, different FmocXaaPsi{PO(OAd)CH(2)}XaaOH building blocks have been prepared, where Fmoc is (fluorenylmethoxy)carbonyl. In this respect, the protection of the hydroxyphosphinyl function in these phosphinic dipeptides by the adamantyl group turns out to be convenient. The phosphinic adamantyl esters are completely stable in basic conditions and can be removed under relatively mild acidic conditions. Using these building blocks, despite the bulkiness of the adamantyl group, no particular problem of coupling was observed during the solid-phase synthesis of phosphinic peptides by the Fmoc strategy. The developed methodology is of particular interest to facilitate the development of potent inhibitors of zinc-metalloproteases.

A phosphinic acid dipeptide analogue to stabilize peptide drugs during their intranasal absorption.

A major challenge in intranasal delivery of peptides is to overcome the enzymatic barrier that limits their absorption. Aminopeptidase inhibitors may be useful for improving systemic delivery of peptide drugs administered nasally. A phosphinic acid dipeptide analogue, a transition-state analogue aminopeptidase inhibitor in which the phosphinate moiety exists in a tetrahedral state mimicking peptides during their enzymatic hydrolysis, was synthesized and tested nasally in situ in rats. This inhibitor was found to inhibit greatly the degradation of the model peptide leucine-enkephalin in the nasal perfusate at less than or equal to 2 microM concentrations. The nasal peptidase hydrolytic activity was reversible after exposure to the inhibitor. This inhibitor has the advantage of efficacy at very low concentrations and reversibility of effects.