Code: ThOC	Time Slot/Poster Number: 10:45-11:10	Session: Drug Discovery
Advances in DOSY Techniques and Applications
Mathias Nilsson
University of Manchester, Manchester, United Kingdom
Abstract
Diffusion-ordered NMR spectroscopy (DOSY) can be a very powerful tool for mixture analysis. In DOSY different rates of diffusion are essential for separating the component spectra, and for it to be effective well resolved signals are highly desirable. Recent developments with increased resolution in both the diffusion and spectral domain are presented together, with novel data processing methods. Particular focus will be on: (i) Matrix-Assisted DOSY (MAD), where differentiation of diffusion rates is achieved by interaction with a matrix (e.g. micelles); (ii) pure shift methods, where the spectral resolution is enhanced by collapsing multiplet structure; and (iii) data processing with multivariate statistics, where covariance in the data is used to extract component spectra.

Code: ThOC	Time Slot/Poster Number: 11:10-11:25	Session: Drug Discovery
Assessment of the Nano-Encapsulated Drug Delivery System for Bone Loss
Qingwen Ni1; Hong Dixon2; yi-xian Qin3
1Texas A&M International University, Laredo, TX; 2Southwest Research Institute, San Antonio, TX; 3State University of New York at Stony Brook, Stony Brook, NY
Abstract
Bone loss, osteoporosis, is recognized as a significant problem in the space programs as well as a major health problem. The objective of this research is to establish a unique localized drug delivery system for bone loss in the critical region by developing a micro-nano encapsulated medicine protocol to accelerate local therapeutic effects, and by using a non-invasive NMR relaxation technique, and X-ray to evaluate the effectiveness of the formation. In this study we have demonstrated an effective, less toxic micro-nano encapsulated drug with designed concentrations, and controlled release-rate formation to prevent bone loss by preparation of enantiomers of promethazine, and employ an animal (rat) disuse hind limb suspension (HLS) rat model to determine the efficacy of the localized delivery.

Code: ThOC	Time Slot/Poster Number: 11:25-11:50	Session: Drug Discovery
Intermolecular Recognition and Drug Design by INPHARMA: How to Deal with Protein Dynamics and More.
Teresa Carlomagno1; Julien Orts1; Benjamin Stauch1; Jennifer Tuma2; Christian Griesinger2; Ulrich Wendt3; Stefan Bartoschek3
1EMBL, Heidelberg, Germany; 2Max Planck Institute for Biophysical Chemistry, Gottingen, Germany; 3Chemical Sciences Structural Biology, Sanofi-Aventis, Germany
Abstract
Small molecules play a fundamental role in the functional regulation of molecular machines. The development of specific binders relies on the availability of structural information for the interaction of the target with low-affinity ligands, identified in screening experiments. The INPHARMA method provides access to the relative binding-mode of low-affinity ligands to a common target. It requires two competitively-binding ligands and a structural model of the apo-receptor. In accordance with structure-based-drug-design workflows, the INPHARMA data are used to select binding modes from computer-generated docking poses. Here we show further developments of INPHARMA and benchmark its performance with respect to the parameters used in the data evaluation, i.e. the structural model of the apo-receptor and the internal dynamics of the binding pocket.

Code: ThOC	Time Slot/Poster Number: 11:50-12:05	Session: Drug Discovery
Structural basis of interactions between HIV-fusion blocking cyanobacterial lectins and gp120 carbohydrates and unusual enzymatic activity of Lectin MVL
Syed Shahzad-ul-Hussan; Carole Bewley
NIH, Bethesda, MD
Abstract
Number of cyanobacterial lectins has been identified in recent years as the potential anti-HIV candidates on account of their ability to potently inhibit the HIV entry to the host cell through carbohydrate-mediated high affinity interactions with HIV envelope glycoprotein gp120. We have described here the structural basis of high affinity interactions between gp120 carbohydrates and two cyanobacterial lectins, and enzymatic ability of one of these two lectins which cleaves the straight chain chitooligosaccharides into monosaccharides using NMR and other biophysical methodologies

Code: ThOC	Time Slot/Poster Number: 12:05-12:30	Session: Drug Discovery
Covariance NMR and Web-Based Analysis of Molecules and Chemical Mixtures
Fengli Zhang1; Steven L. Robinette1; David Snyder2; Lei Bruschweiler-Li1; Rafael Bruschweiler1
1Florida State University & NHMFL, Tallahassee, FL; 2William Paterson University, Wayne, New Jersey
Abstract
Elucidation of the composition of complex biological samples is a main focus of systems biology and metabolomics. In cases where the analysis of 1D NMR spectra is ambiguous, efficient and reliable 2D methods are required. We have explored the use of covariance NMR and its generalizations for this task to produce high-resolution spectra using a small number of increments. Homonuclear and heteronuclear covariance TOCSY spectra can be deconvoluted into 1D spectra of individual spin systems (DemixC), which can be efficiently screened against NMR spectral databases. Based on these principles, we have set up the COLMAR web server (http://spinportal.magnet.fsu.edu), which performs covariance processing, DemixC, and database query and which will be demonstrated for various examples.