Physical Sciences and Mathematics Commons^™

Synthesis And Performance Of Novel Supramolecular Tools For Single-Particle Cryogenic Electron Microscopy And Drug And Gene Delivery, Kyle J. Wright

Open Access Dissertations

High-resolution biomacromolecular structure elucidation is fundamentally important to structure-based drug design and basic research into complex biochemical processes. Cryo-EM is an emerging alternative to XRD and NMR that is complementary in many ways relative to XRD and NMR. Materials approaches to cryo-EM are anticipated to greatly facilitate the cryo-EM process, allowing progress toward a more high-throughput application of cryo-EM to address challenges in structural biology. ^ Various affinity-based approaches inspired by approaches previously introduced for 2D crystallization were developed for facilitation of cryo-EM. A library of affinity lipopolymer constructs were synthesized consisting of lipopolymers of various PEG molecular weights conjugated …

Continued Progress Towards Efficient Syntheses Of Cephalostatin North 1 Analogs, Daniel Preston Jamieson

Open Access Dissertations

Jamieson, Daniel P. Ph.D., Purdue University, December 2013. Continued Progress Towards Efficient Syntheses of Cephalostatin North 1 Analogs. Major Professor: PhilipL. Fuchs.

The cephalostatins and ritterazines represent an intriguing class of marine natural products in both structure and biological activity, and the progress towards the synthesis of high valued analogs with a focus on process orientated methodology is described herein. Included in the pages to follow, is the further advancement of the `Red-Ox' strategy toward the highly efficient synthesis of 25-epi-4,15-dihydro-North 1, Chapter 2. A short review focusing on the earlier efforts toward the main synthetic challenges of North 1 …

Synthesis Of Novel Isoprenoid Diphosphate Analogs As Chemical Tools To Investigate Protein Geranylgeranylation, Kayla Jo Temple

Open Access Dissertations

Many proteins require prenylation in order to be biologically functional. Some such proteins include the small Ras and Rho GTPase superfamilies, nuclear lamins A and B, and the kinesin motor proteins CENP-E and F. Prenyltransferase (PTase) inhibition is currently being explored as a possible treatment not only for cancer but for a wide variety of other diseases.

Clinical studies revealed that the effectiveness of farnesyltransferase inhibitors (FTIs) to treat Ras-dependent tumors is determined by which isoform of Ras is overactive. Unfortunately the majority of Ras-dependent tumors have a mutation in either the N- or K-Ras isoforms; both of these isoforms …