Bianca R. Sculimbrene

Lanthanide-binding tags with unnatural amino acids: sensitizing Tb3+ and Eu3+ luminescence at longer wavelengths.

Lanthanide-binding tags (LBTs) are small, genetically encoded, versatile protein fusion partners that selectively bind lanthanide ions with high affinity. The LBT motif features a strategically positioned tryptophan residue that sensitizes Tb3+ luminescence upon excitation at 280 nm. Herein, we describe the preparation of new LBT peptides that incorporate unnatural amino acids in place of tryptophan, and which sensitize both Tb3+ and Eu3+ luminescence at lower energies. We also report the semisynthesis of proteins tagged with these new LBTs using native chemical ligation. This expands the scope of LBTs and will enable their wider use in luminescence applications.

Silatranyl-nucleosides: transition state analogues for phosphoryl transfer reactions

Abstract A novel class of compounds that contain a silatrane moiety attached to or incorporated within a nucleoside is described. These compounds are transition state analogues for phosphoryl transfer reactions and as such have potential antiviral and anticancer properties. The two-step synthesis of 3′- O -(trimethyl)silatranylthymidine ( 1 ) in 17% yield is reported. The aqueous half-life of 1 was determined to be 62 h by 1 H NMR. The syntheses of three 2′,3′-protected-5′- O -silatranyladenosines in 25–55% yields are also described.

Synthesis of a D-Ala-D-Ala peptide isostere via olefin cross-metathesis and evaluation of vancomycin binding.

The alkene peptide isostere for the d-Ala-d-Ala dipeptide was synthesized via a convergent approach utilizing olefin cross-metathesis. The new isostere was then evaluated for binding to the last resort antibiotic, vancomycin. The alkene isostere exhibited a K(D)=90 microM in comparison to the native peptide (K(D)=2.3 microM) and Lac mutant (K(D)=2300 microM). This study demonstrates that loss of binding in vancomycin resistant strains as a result of a d-Ala to d-Lac mutation is from both the loss of a crucial hydrogen bond and introduction of a repulsive lone pair interaction.