Torrey Pines Institute for Molecular Studies

About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: Antigen & T cell. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.

Synthesis and Characterization of a Dual Kappa-Delta Opioid Receptor Agonist Analgesic Blocking Cocaine Reward Behavior

Abstract: 3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids We present the synthesis and pharmacological evaluation of five analogs of IBNtxA The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents The structural modifications resulted in analogs with picomolar affinities for opioid receptors The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 033 mg/kg) compared with morphine, mediated through the activation of kappa- and delta-opioid receptors Despite its kappa agonism, this lead derivative did not cause place aversion or preference in mice in a place-conditioning assay, even at doses 3 times the analgesic ED50 However, pretreatment with the lead compound prevented the reward behavior associated with cocaine in a conditioned place preference assay Together, these results suggest the promise of dual acting kappa- and delta-opioid receptor agonists as analgesics and treatments for cocaine addiction

Evolutionary optimization, backpropagation, and data preparation issues in QSAR modeling of HIV inhibition by HEPT derivatives.

Abstract: Artificial neural networks (ANNs) can be utilized to generate predictive models of quantitative structure-activity relationships between a set of molecular descriptors and activity. Evolutionary computation provides a means to appropriately search for the set of weights and bias terms associated with artificial neural networks that minimize selected functions of the error between the actual and desired outputs. This method is demonstrated by evolutionary training of artificial neural networks capable of predicting anti-HIV activity for a set of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives. The results of this work further confirm the growing indication that evolutionary computation can outperform backpropagation as a method of artificial neural network training. The results also indicate the degree to which bias in the initial training and testing data can affect performance and the importance of bootstrapping.

Toward targeted oral vaccine delivery systems: selection of lectin mimetics from combinatorial libraries.

Abstract: Purpose Various lectins bind specifically to oligosaccharides on intestinal cells Exploiting this specificity, Ulex europaeus agglutinin I (UEA1) has been used as a ligand for targeted oral vaccine delivery to M cells (antigen-presenting cells) in follicle-associated epithelium In this study we characterized compounds identified from mixture-based positional scanning synthetic combinatorial libraries, which mimic UEA1 and, thus, may have properties applicable to targeted drug delivery