Nanoassisted Laser Desorption-Ionization-MS Imaging of Tumors

The ability of nanoassisted laser desorption-ionization mass spectrometry (NALDI-MS) imaging to provide selective chemical monitoring with proper spatial distribution of lipid profiles from tumor tissues after plate imprinting has been tested. NALDI-MS imaging identified and mapped several potential lipid biomarkers in a murine model of melanoma tumor (inoculation of B16/F10 cells). It also confirmed that the in vivo treatment of tumor bearing mice with synthetic supplement containing phosphoethanolamine (PHO-S) promoted an accentuated decrease in relative abundance of the tumor biomarkers. NALDI-MS imaging is a matrix-free LDI protocol based on the selective imprinting of lipids in the NALDI plate followed by the removal of the tissue. It therefore provides good quality and selective chemical images with preservation of spatial distribution and less interference from tissue material. The test case described herein illustrates the potential of chemically selective NALDI-MS imaging for biomarker discovery.     

Synthesis and biological properties of new 2beta-alkyl- and 2beta-aryl-3-(substituted phenyl)tropane derivatives: stereochemical effect of C-3 on affinity and selectivity for neuronal dopamine and serotonin transporters

In our efforts to identify molecules that might act as cocaine antagonists or cocaine partial agonists, we have been involved in efforts to further elucidate the nature of cocaine's binding to the dopamine transporter (DAT) through strategic modifications of its structure. In the case of the substituent located at the 2-position of the tropane ring, studies have revealed the ability of the transporter to accommodate groups of diverse structure, including ester, ketone, alkyl, alkenyl, heterocyclic, and aryl substituents, without loss of DAT binding affinity. In the present study, we report our results pertaining to the ability of the DAT to accommodate the WIN-type structures possessing alkyl or aryl groups at the 2-position and which adopt either a chair or a boat conformation of the tropane ring. Moreover, we discuss the influence of the stereochemistry of these compounds in their selectivity for the DAT versus the serotonin transporter (5HTT). Additionally, we point out the importance of using Ki values rather than IC50 values when making such comparisons of transporter selectivity. One of the most interesting compounds identified in the present work is a 2, 3-diaryltropane 22 in a boat conformation that is highly selective (69-fold) for the DAT over the 5HTT. The ability to prepare this compound as well as related structures by our oxidopyridinium betaine-based dipolar cycloaddition strategy further underscores the versatility of this particular chemical approach to the preparation of diverse tropane analogues. The use of the optically pure olefin p-tolyl vinyl sulfoxide as the dipolarophile in this reaction allows access to these novel tropanes in nonracemic form.     

Synthesis and metabotropic glutamate receptor activity of a 2-aminobicyclo[3.2.0]heptane-2,5-dicarboxylic acid, a molecule possessing an extended glutamate conformation

A photochemical approach to the synthesis of the aminobicycloheptane 6a is reported. This compound assumes an extended glutamate conformation, and for this reason was created to further probe the structural features relevant to achieving selectivity for the subtypes of the metabotropic glutamate family of receptors.     

Cyclic RGD‐Containing Functionalized Azabicycloalkane Peptides as Potent Integrin Antagonists for Tumor Targeting

Vitronectin receptors α _v β ₃ and α _v β ₅ have emerged as potential therapeutic targets for the treatment of osteoporosis, restenosis, ocular disease, tumor‐induced angiogenesis, metastasis, and sickle‐cell anemia. Among a collection of compounds, a new potent integrin antagonist was synthesized, and its binding toward the α_vβ₃ and α_vβ₅ receptors was evaluated. This molecule is a suitable candidate as a vector for therapeutics and diagnostics.

     

Spray Chilling Microencapsulation of <Emphasis Type="Italic">Lactobacillus acidophilus</Emphasis> and <Emphasis Type="Italic">Bifidobacterium animalis</Emphasis> subsp. <Emphasis Type="Italic">lactis</Emphasis> and Its Use in the Preparation of Savory Probiotic Cereal Bars

The use of probiotic microorganisms has been limited by the difficulty of maintaining their viability during processing and throughout the product’s shelf life. This study evaluated the viability of microencapsulating Lactobacillus acidophilus (LA) and Bifidobacterium animalis subsp. lactis (BL) using the spray chilling technique to add them to savory cereal bars. The results showed that spray chilling generated a powder that was composed of smooth and continuous spheres with low moisture content and low water activity. The microencapsulated microorganisms exhibited a storage viability at least of 90 days as microparticles and in savory cereal bars, and their counts were superior to those resulting from other methods of adding activated and lyophilized probiotics to savory cereal bars. Thus, microparticles prepared by spray chilling are good vehicles for incorporating probiotics into cereal bars and have the potential to release the probiotics in the consumers’ intestines by means of fat digestion. Savory cereal bars that did and did not contain probiotics exhibited no differences in sensorial acceptance or commercial potential.