An improved synthesis of a haptenic heroin surrogate 1 (6-AmHap) is reported. The intermediate needed for the preparation of 1 was described in the route in the synthesis of 2 (DiAmHap). A scalable procedure was developed to install the C-3 amido group. Using the Boc protectng group in 18 allowed preparation of 1 in an overall yield of 53% from 4 and eliminated the necessity of preparing the diamide 13. Hapten 1 was conjugated to tetanus toxoid and mixed with liposomes containing monophosphoryl lipid A as an adjuvant. The 1 vaccine induced high anti-1 IgG levels that reduced heroin-induced antinociception and locomotive behavioral changes following repeated subcutaneous and intravenous heroin challenges in mice and rats. Vaccinated mice had reduced heroin-induced hyperlocomotion following a 50 mg/kg heroin challenge. The 1 vaccine-induced antibodies bound to heroin and other abused opioids, including hydrocodone, oxycodone, hydromorphone, oxymorphone, and codeine.

DNA-nanoparticle conjugates are important tools in nanobiotechnology. Knowing the orientation, function, and length of DNA on nanoparticle surfaces at low nanomolar concentrations under physiological conditions is therefore of great interest. Here, we investigate the conformation of a 31 nucleotides (nt) long DNA attached to a semiconductor quantum dot (QD) via Forster resonance energy transfer (FRET) from Tb-DNA probes hybridized to different positions on the QD-DNA. Precise Tb-to-QD distance determination from 7 to 14 nm along 26 nt of the peptide-appended QD-DNA was realized by time-resolved FRET spectroscopy. The FRET nanoruler measured linear single-stranded (ssDNA) and double-stranded (dsDNA) extensions of ∼0.15 and ∼0.31 nm per base, reflecting the different conformations. Comparison with biomolecular modeling confirmed the denser conformation of ssDNA and a possibly more flexible orientation on the QD surface, whereas the dsDNA was fully extended with radial orientation. The temporally distinct photoluminescence decays of the different DNA-FRET configurations were used for prototypical DNA hybridization assays that demonstrated the large potential for extended temporal multiplexing. The extensive experimental and theoretical analysis of 11 different distances/configurations of the same QD-DNA conjugate provided important information on DNA conformation on nanoparticle surfaces and will be an important benchmark for the development and optimization of DNA-nanobiosensors.

Accumulating studies by many groups have found consistent enhancement in a wide variety of enzyme activities when they are displayed around nanoparticles.

Extension of the asymmetric Pictet-Spengler reaction to bulkier N -alkylated tryptophan derivatives resulted in an improved stereospecific access to the key bicyclo[3.3.1]nonane core of bioactive C-19 methyl substituted sarpagine/macroline/ajmaline indole alkaloids with excellent diastereoselectivity by internal asymmetric induction. Complete stereocontrol of the C-19 methyl function in either the α- or β-configuration was achieved, which enables the total synthesis of any member from this group of thirty alkaloids. We report herein, the total synthesis of macrocarpines (A-C) 1-3, talcarpine 4, N(4)-methyl-N(4),21-secotalpinine 5, dihydroperaksine 8 and deoxyperaksine 9.

Three C9 substituted N-phenethyl-5-phenylmorphans were found to be extremely G-protein biased potent mu opioid receptor partial agonists that did not recruit beta-arrestin at all in both the PathHunter assay and in the Tango assay.