Reversible metal-dependent destabilization and stabilization of a stem-chelate-loop probe binding to an unmodified DNA target.

Herein, we report the discovery of a novel DNA probe with a stem-chelate-loop structure, wherein the stability of the probe-target duplex can be modulated lower or higher using a narrow concentration range of dilute transition metal ions (0.1-10 μM). Oligonucleotide probes containing two terpyridine (TPY) ligands separated by 15 bases of single-stranded DNA, with or without a flanking 5 base self-complementary DNA stem, were tested in thermal transition studies with linear target DNA and varying amounts of ZnCl(2).

Intestinal transport of aminopterin enantiomers in dogs and humans with psoriasis is stereoselective: evidence for a mechanism involving the proton-coupled folate transporter.

N-[4-[[(2,4-diamino-6-pterdinyl)methyl]amino]benzoyl]-L/D-glutamic acid (L/D-AMT) is an investigational drug in phase 1 clinical development that consists of the L-and D-enantiomers of aminopterin (AMT). L/D-AMT is obtained from a novel process for making the L-enantiomer (L-AMT), a potent oral antiinflammatory agent. The purpose of these studies was to characterize oral uptake and safety in the dog and human of each enantiomer alone and in combination and provide in vitro evidence for a mechanism of intestinal absorption.

Clusters of ligands on dendrimer surfaces.

The development of methodology that is designed to allow a significant increase in the patterning and in the functionalization of the dendrimer is the ultimate goal of the research described here. Glycoside clusters based on TRIS were formed using click chemistry and were attached to PAMAM dendrimers. A series of dendrimers bearing tris-mannoside and an ethoxyethanol group was synthesized, and the binding interactions of these dendrimers with Concanavalin A were evaluated using inhibition ELISAs.

Synthesis and evaluation of phosphopeptides containing iminodiacetate groups as binding ligands of the Src SH2 domain.

Phosphopeptide pTyr-Glu-Glu-Ile (pYEEI) has been introduced as an optimal Src SH2 domain ligand. Peptides, Ac-K(IDA)pYEEIEK(IDA) (1), Ac-KpYEEIEK (2), Ac-K(IDA)pYEEIEK (3), and Ac-KpYEEIEK(IDA) (4), containing 0-2 iminodiacetate (IDA) groups at the N- and C-terminal lysine residues were synthesized and evaluated as the Src SH2 domain binding ligands. Fluorescence polarization assays showed that peptide 1 had a higher binding affinity (K(d) = 0.

Snap-to-it probes: chelate-constrained nucleobase oligomers with enhanced binding specificity.

We describe snap-to-it probes, a novel probe technology to enhance the hybridization specificity of natural and unnatural nucleic acid oligomers using a simple and readily introduced structural motif. Snap-to-it probes were prepared from peptide nucleic acid (PNA) oligomers by modifying each terminus with a coordinating ligand. The two coordinating ligands constrain the probe into a macrocyclic configuration through formation of an intramolecular chelate with a divalent transition metal ion.

Cyanovirin-N binding to Manalpha1-2Man functionalized dendrimers.

Manalpha1-2Man functionalized G(3) and G(4)-PAMAM dendrimers have been synthesized and characterized by MALDI-TOF MS and NMR spectroscopy. Precipitation assays to assess the binding of the dimannose-functionalized dendrimers to Cyanovirin-N, a HIV-inactivating protein that blocks virus-to-cell fusion through high mannose mediated interactions, are presented.

Altering the strength of lectin binding interactions and controlling the amount of lectin clustering using mannose/hydroxyl-functionalized dendrimers.

Protein-carbohydrate interactions play a critical role in many biological recognition events. Multivalent therapeutic agents that utilize protein-carbohydrate interactions have proven difficult to design, primarily because the fundamental requirements of protein-carbohydrate interactions are not well understood. Here, we report a systematic study of the effect on lectin binding of varying the loading of mannose surface residues on generations three through six PAMAM dendrimers.

Heterogeneously functionalized dendrimers.

Significant timely advances have been made in the synthesis of heterogeneously functionalized dendrimers. Convergent, divergent and other functionalization techniques have been used to create a variety of complex dendrimer motifs with more than one type of surface group. Synthetic advances, as well as pertinent applications of heterogeneously functionalized dendrimers, are reviewed.