| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000436435 |
| 005 | | 20200228143708 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781392276709 |
| 035 | |
▼a (MiAaPQ)AAI13809114 |
| 035 | |
▼a (MiAaPQ)colostate:15333 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 540 |
| 100 | 1 |
▼a Walker, Susanne N. |
| 245 | 10 |
▼a Engineering and Evolving Helical Proteins That Improve in Vivo Stability and Inhibit Entry of Enfuvirtide-Resistant HIV-1. |
| 260 | |
▼a [S.l.]:
▼b Colorado State University.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 146 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 80-12, Section: B. |
| 500 | |
▼a Publisher info.: Dissertation/Thesis. |
| 500 | |
▼a Advisor: Kennan, Alan. |
| 502 | 1 |
▼a Thesis (Ph.D.)--Colorado State University, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 520 | |
▼a Methods for the stabilization of well-defined helical peptide drugs and basic research tools have received considerable attention in the last decade. Enfuvirtide is a 36-residue chemically synthesized helical peptide that targets the viral gp41 protein and inhibits viral membrane fusion. Enfuvirtide-resistant HIV, however, has been prolific, and this peptide therapy requires daily injection due to proteolytic degradation.In this dissertation I have developed a method for stabilizing helical peptide therapeutics termed helix-grafted display proteins. These consist of the HIV-1 gp41 C-peptide helix grafted onto Pleckstrin Homology domains. Some of these earlier protein biologics inhibit HIV-1 entry with modest and variable potencies (IC50 190 nM - >1 關M). After optimization of the scaffold and the helix, our designer peptide therapeutic potently inhibited HIV-1 entry in a live-virus assay (IC50 1.9-12.4 nM). Sequence optimization of solvent-exposed helical residues using yeast display as a screening method led to improved biologics with enhanced protein expression in Escherichia coli (E. coli, a common bio-expression host), with no appreciable change in viral membrane fusion suppression. Optimized proteins suppress the viral entry of a clinically-relevant double mutant of HIV-1 that is gp41 C-peptide sensitive and Enfuvirtide-resistant. Protein fusions engineered for serum-stability also potently inhibit HIV-1 entry. |
| 590 | |
▼a School code: 0053. |
| 650 | 4 |
▼a Chemistry. |
| 690 | |
▼a 0485 |
| 710 | 20 |
▼a Colorado State University.
▼b Chemistry. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 80-12B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0053 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15490568
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |