عنوان
پدید آورنده
موضوع
رده
کتابخانه
محل استقرار
شماره کتابشناسی ملی
شماره
TL51924
زبان اثر
زبان متن نوشتاري يا گفتاري و مانند آن
انگلیسی
عنوان و نام پديدآور
عنوان اصلي
Detection and Perturbation of MicroRNAs Using Synthetic Chemical Probes
نام عام مواد
[Thesis]
نام نخستين پديدآور
Ankenbruck, Nicholas Michael
نام ساير پديدآوران
Deiters, Alexander
وضعیت نشر و پخش و غیره
نام ناشر، پخش کننده و غيره
University of Pittsburgh
تاریخ نشرو بخش و غیره
2019
يادداشت کلی
متن يادداشت
525 p.
یادداشتهای مربوط به پایان نامه ها
جزئيات پايان نامه و نوع درجه آن
Ph.D.
کسي که مدرک را اعطا کرده
University of Pittsburgh
امتياز متن
2019
یادداشتهای مربوط به خلاصه یا چکیده
متن يادداشت
MicroRNAs (miRNAs) are small, non-coding RNA molecules capable of regulating protein expression in cells via binding to a complementary sequence within the 3' untranslated region (3' UTR) or coding domain sequence (CDS) of target messenger RNAs (mRNAs), thereby inducing translational repression and ultimately mRNA degradation. As such, its unsurprising that dysregulation of miRNAs has been implicated in a wide range of diseases in humans, including cancer. While regulation of miRNAs has largely been mediated by oligonucleotide reagents, current technologies exhibit limitations in terms of stability and pharmacological properties. In contrast, small molecules possess many advantageous qualities as tools to perturb miRNA function, including fast activity, systematic delivery, and enhanced cell permeability. Two luciferase-based reporters were developed into a cell-based assay employed in separate high-throughput screens of >300,000 compounds to identify selective small molecule modifiers of miR-21 or miR-122 function. The work presented herein discusses validation of oxadiazole, ether-amide, and N-acylhydrazone miR-21 inhibitors as well as sulfonamide and methanone inhibitors of miR-122 function identified in their respective high-throughput screens. In addition to secondary assays to confirm function and specificity of the lead molecules, structure-activity relationship (SAR) studies were carried out in order to determine important structural features of each scaffold and to attempt to improve their activity. Moreover, preliminary functional assays were carried out to evaluate therapeutic potential of improved molecules identified through the SAR study. Collaborations with start-up companies to discover small molecule inhibitors of miRNA processing are also presented. Additionally, delivery of DNA logic devices capable of recognizing miRNAs in cells or releasing a small molecule output in response to miRNA inputs are discussed. Optical regulation of chemical tools using light affords spatial and temporal control over biological processes and as such, a second-generation caged promoter was incorporated into a plasmid to afford optical control of transcription. Finally, methods for delivery of γ-modified peptide nucleic acids (PNAs) and morpholino oligomers into mammalian cells for use as splice-switching oligonucleotides or anti-miRNA agents were explored.
اصطلاحهای موضوعی کنترل نشده
اصطلاح موضوعی
Biochemistry
اصطلاح موضوعی
Cellular biology
اصطلاح موضوعی
Chemistry
نام شخص به منزله سر شناسه - (مسئولیت معنوی درجه اول )
مستند نام اشخاص تاييد نشده
Ankenbruck, Nicholas Michael
نام شخص - ( مسئولیت معنوی درجه دوم )
مستند نام اشخاص تاييد نشده
Deiters, Alexander
شناسه افزوده (تنالگان)
مستند نام تنالگان تاييد نشده
University of Pittsburgh
دسترسی و محل الکترونیکی
نام الکترونيکي
مطالعه متن کتاب وضعیت انتشار
فرمت انتشار
p
اطلاعات رکورد کتابشناسی
نوع ماده
[Thesis]
کد کاربرگه
276903
اطلاعات دسترسی رکورد
سطح دسترسي
a
تكميل شده
Y
