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Type of Document	Dissertation
Author	Qi, Xin
Author's Email Address	xqi AT its.caltech.edu
URN	etd-05272005-133323
Persistent URL	http://resolver.caltech.edu/CaltechETD:etd-05272005-133323
Title	Unnatural amino acid incorporation to rewrite the genetic code and RNA-peptide interactions
Degree	PhD
Option	Chemistry
Advisory Committee	Advisor Name Title Peter B. Dervan Committee Chair Richard W. Roberts Committee Member Robert H. Grubbs Committee Member Stephen L. Mayo Committee Member
Keywords	suppression puromycin synthetase inhibitor N-peptide acridine
Date of Defense	2005-05-19
Availability	mixed
Abstract My general research direction is the interface between organic chemistry and biology. Interesting biological systems inspire target-oriented organic synthesis, new methodology development, and molecular design of novel materials. On the other hand, chemical synthesis prepares important biologically active compounds to be used in understanding involved mechanism and engineering biological systems. We designed and synthesized a series of peptide-acridine conjugates based on the modular design principle to target RNA structures. Some of the peptide-acridine conjugates have substantially improved RNA-binding affinity and specificity relative to the peptide alone. We also generated various high-affinity inhibitors of the tRNA synthetases—aminoacyl sulfamide to create synthetic blanks in our translation extracts. The gaps were filled with chemically aminoacylated orthogonal tRNAs. This unnatural strategy enables peptides and proteins to be constructed containing a single novel residue at specific locations and will facilitate the mRNA display-based protein selection. To test the versatility of ribosome, we have constructed a series of puromycin analogs with natural and unnatural amino acids side chains and tested the effects of side chain characteristics of amino acid moiety on the activity of puromycin analogs. We found that amino acids of different stereo characteristics can be incorporated via puromycin route, and larger hydrophobic amino acids render higher potency. Overall, these efforts demonstrate the successful use of a combination of molecular design as an efficient and facile method for generating new solutions to biological problems.
Files	Filename       Size       Approximate Download Time (Hours:Minutes:Seconds)     28.8 Modem   56K Modem   ISDN (64 Kb)   ISDN (128 Kb)   Higher-speed Access  xqicover.pdf 93.49 Kb 00:00:25 00:00:13 00:00:11 00:00:05 < 00:00:01 There are 5 files which have been withheld at the author's request. indicates that a file or directory is accessible from the campus network only and must not be distributed to non-campus persons.