Synthesis of Small Molecules for the Modulation of Protein-protein Interactions and the Study of Lipid Droplet Degradation PDF Download
Are you looking for read ebook online? Search for your book and save it on your Kindle device, PC, phones or tablets. Download Synthesis of Small Molecules for the Modulation of Protein-protein Interactions and the Study of Lipid Droplet Degradation PDF full book. Access full book title Synthesis of Small Molecules for the Modulation of Protein-protein Interactions and the Study of Lipid Droplet Degradation by Pascal Markus Engelhardt. Download full books in PDF and EPUB format.
Author: Pascal Markus Engelhardt
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
Author: Pascal Markus Engelhardt
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Get Book Here
Book Description
Author: Herbert Waldmann
Publisher: Springer Science & Business Media
ISBN: 3662053144
Category : Medical
Languages : en
Pages : 248
Get Book Here
Book Description
Based on the international workshop on 'Small Molecule - Protein Interactions' held in Berlin, April 24-26, 2002, researchers from industry and academic laboratories describe novel and efficient ways selecting promising new drug targets and developing small molecule inhibitors against them. The structure of the book corresponds to the different aspects of the drug discovery process. All chapters are written by leading experts in the field, who present and discuss the most recent state-of-the-art tools and techniques for the development of novel drugs. The value of the book lies in surveying and summarizing the approaches taken by different companies and institutions giving the reader a balanced view on the use of the latest techniques on the one hand and experience-based assistance in selecting appropriate tools for their own work on the other hand.
Author: Florian Nietzold
Publisher:
ISBN:
Category :
Languages : de
Pages :
Get Book Here
Book Description
Author: Christian Lis
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Author: Xu Han
Publisher:
ISBN:
Category : Calcium channels
Languages : en
Pages : 276
Get Book Here
Book Description
Protein-protein interactions play a crucial role in a wide range of biological processes. Research on the design and synthesis of small molecules to modulate these proteinprotein interactions can lead to new targets and drugs to modulate their function. In chapter one, we discuss the design and synthesis of small molecules to probe a proteinprotein interaction in a voltage-gated Ca2+ channel. Virtual screening identified a compound (BTT-3) that contained a 3,4-dihydro-3,4'-pyrazole core. This compound had modest biological activity when tested in a fluorescence polarization (FP) assay. The synthetic route to BTT-3 consisted of six steps. In addition, analogs of BTT-3 were made for a structure-activity study to establish the importance of a carboxylate moiety. We also synthesized a biotinylated benzophenone photo-affinity probe and linked it to BTT-3 to identify additional protein targets of the compound. In Chapter two, small-molecule antagonists targeting uPA-uPAR protein-protein interaction are presented. A total of 500 commercially-available compounds were previously identified by virtual screening and tested by a FP assay. Three classes of compounds were found with biological activity. The first class of compounds contains pyrrolidone core structures represented by IPR- 1110, the second class has a novel pyrrolo[3,4-c]pyrazole ring system, represented by xv IPR-1283 and the last series had compounds with a 1,2-disubstituted 1,2- dihydropyrrolo[3,4-b]indol-3(4H)-one core structure, represented by IPR-540. Each of these three compounds were synthesized and assessed by FP and ELISA assays. A binding mode of IPR-1110 with uPA was subsequently proposed. Based on this binding mode, another 61 IPR-1110 derivatives were synthesized by us to illustrate the SAR activity. Analogs of the other two series were also synthesized.
Author: Jennifer J. McManus
Publisher: Humana
ISBN: 9781493996803
Category : Science
Languages : en
Pages : 266
Get Book Here
Book Description
This volume explores experimental and computational approaches to measuring the most widely studied protein assemblies, including condensed liquid phases, aggregates, and crystals. The chapters in this book are organized into three parts: Part One looks at the techniques used to measure protein-protein interactions and equilibrium protein phases in dilute and concentrated protein solutions; Part Two describes methods to measure kinetics of aggregation and to characterize the assembled state; and Part Three details several different computational approaches that are currently used to help researchers understand protein self-assembly. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Protein Self-Assembly: Methods and Protocols is a valuable resource for researchers who are interested in learning more about this developing field.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
The design of small molecules toward the modulation of a specific molecular biosystem was explored in two distinctive parts: (PART A) Design of Carbocyclic Peptide Analogues to Counteract a Pre-Determined RNA-Protein Interaction, and (PART B) Design of Imidazole Derivatives toward Biofilm Modulation. The design of carbocyclic analogues was particularly relevant to RNA-protein interactions due to the ever-raising evidence of RNA's essential role in cellular functions and high affinity of cyclic peptides with oligonucleotides. A facile route toward the synthesis of carbocyclic heptapeptides counterparts of bTAR RNA cysteine-constrained peptide binders, P1 and P2, was developed through the exploration of ring-closing metathesis conditions with four metathesis catalysts (Grubbs 1st, 2nd and Hoveyda-Grubbs 1st, 2nd generations) on the (1) resin-free, and (2) resin-bound linear di-olefin precursors. Classic Fmoc chemistry was employed to generate the di-olefin precursors prior to cyclization. Optimum ring closing conditions for this crucial step were explored in order to generate the substantial 29-membered macrocyles, and the results of this study are described in PART A. The design of imidazole derivatives was particularly relevant toward biofilm modulation studies due to the ever-increasing number of untreatable biofilm-derived bacterial infections. Imidazole marine alkaloids were found to be great anti-biofilm agents particularly the 2-aminoimidazole scaffold that is embedded within the natural product bromoageliferin. Thus, we sought to explore further 2-aminoimidazole scaffolds to establish structure activity relationships and to provide insight on the mechanism behind the mysterious biofilm formation as entailed in PART B.
Author: Sumit Mittal
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Author: Eunhwa Ko
Publisher:
ISBN:
Category :
Languages : en
Pages :
Get Book Here
Book Description
Protein-protein interactions (PPIs) are attractive targets because of their therapeutic potential. One approach to design small molecules that can disrupt the PPIs is to use structural information of proteins. With this approach, triazole-based peptidomimetics that mimic beta-turn hot-spot regions in neurotrophins were synthesized. The monovalent mimics were assembled into bivalent mimics via a combinatorial method. Three different bivalent mimics were prepared for different studies. Bivalent mimics with long-linkers bound to TrkA or TrkC receptor and showed partial antagonism for the receptors. Other mimics were conjugated with cytotoxic compounds and they were used for TrkC targeted drug delivery. The last group of bivalent mimics previously showed targeted delivery effects for pancreatic cancer cells. In this study, we synthesized Eu-chelated bivalent mimics to perform a competitive binding assay for pancreatic cancer cells. Previous research in our group focused on design of secondary structures' mimics on rigid scaffolds as "minimalist mimics." We sought to establish structural design criteria for the minimalist mimics, and we wanted to propose that sets of such compounds could mimic local pairs of amino acids in any secondary structures as "universal peptidomimetics." Thus, we designed five compounds, such as oxazoline-, pyrrole-, dyine- "kinked" and "linear" bistrizole-based peptidomimetics, and performed molecular modelings, DFT calculations, and QMD for them to validate our hypothesis. On the concepts of "minimalist mimics" and "universal peptidomimetics," we developed the C alpha? C beta vector matching program to evaluate preferred orientations of C alpha - C beta coordinates for secondary structures. We applied the program to omegatides and pyrrolinone-pyrrolidine oligomers. The compounds matched better with strands than for helices. We expanded the C alpha? C beta vector matching idea to a method that ranks preferred conformations of small molecules on any combination of three interface side-chains in all structurally characterized PPIs. We developed a PDB mining program (explores key orientation, EKO) to do this, and EKO applied to pyrrolinone-pyrrolidine oligomers to find targets. EKO found several interesting targets, such as AICAR Tfase, GAPDH, and HIV-1 protease. HIV-1 dimerization inhibition and Zhang-Poorman kinetic assays were performed to validate our hypothesis, and the results showed that pyrrolinone-pyrrolidine derivatives inhibited HIV-1 dimerization.
Author: Bruce Alberts
Publisher:
ISBN: 9780815332183
Category : Cytology
Languages : en
Pages : 0
Get Book Here
Book Description
