Facile rhenium–peptide conjugate synthesis using a one-pot derived Re(CO)₃ reagent

Abstract

We have synthesized two Re(CO)3-modified lysine complexes (1 and 2), where the metal is attached to the amino acid at the Nε position, via a one-pot Schiff base formation reaction. These compounds can be used in the solid phase synthesis of peptides, and to date we have produced four conjugate systems incorporating neurotensin, bombesin, leutenizing hormone releasing hormone, and nuclear localization sequence. We observed uptake into human umbilical vascular endothelial cells as well as differential uptake depending on peptide sequence identity, as characterized by fluorescence and rhenium elemental analysis.

Using hydrazine to link ferrocene with Re(CO)3: A modular approach

“…Additionally, ferrocene and Re(CO) 3 compounds can be readily incorporated into molecules for potential materials applications. In work from our laboratories, we have functionalized proteins and peptides with the Re(CO) 3 unit [23,24], and have appended the ferrocene unit to chromophores like porphyrin, phthalocyanine, BODIPY, azaBODIPY and the recent BOPHY fluorophore [25–29]. …”

An Organometallic Isostere of an Amino Acid

“…13−19 Rhenium tricarbonyl compounds can be chiral-at-metal in the presence of asymmetric coordination geometries, but to date, such chemistry has also not been explored. 20,21 We hypothesized that we could make a chiral-at-metal fac-Re(CO) 3 complex using a simple synthetic protocol and the resultant compound would act as an isostere of an amino acid. In this report, we present a strategy for the straightforward synthesis of fac-Re(CO) 3 amino acid isosteres using a simple bipyridine chelate.…”

“…Chiral organometallic complexes are commonly used in applications ranging from organic synthesis − to medicinal inorganic chemistry. − Chirality in organometallics is typically achieved by incorporation of a chiral ligand at a metal center. − However, transition metal complexes can be chiral at the metal itself, but this chemistry has not been expansively investigated. − Rhenium tricarbonyl compounds can be chiral-at-metal in the presence of asymmetric coordination geometries, but to date, such chemistry has also not been explored. , We hypothesized that we could make a chiral-at-metal fac -Re­(CO) 3 complex using a simple synthetic protocol and the resultant compound would act as an isostere of an amino acid. In this report, we present a strategy for the straightforward synthesis of fac -Re­(CO) 3 amino acid isosteres using a simple bipyridine chelate.…”

“…To probe the utility of these organometallic isosteres, we decided to incorporate the isostere fac -[Re­(bpy)­(CO) 3 ]Cl into a simple tripeptide using solid-phase peptide synthesis (SPPS) methods. , Using a Rink amide resin with the HBTU coupling/Fmoc protection strategy, we constructed a gly-Re­(aa-bpy)­(CO) 3 X-gly tripeptide. We chose glycine because we hypothesized that we could resolve a racemic tripeptide mixture using the rhenium center alone.…”