Doctor of Philosophy (Ph.D.)
Degree Granting Department
Mark Mclaughlin, Ph.D.
David Morse, Ph.D.
Jianfeng Cai, Ph.D.
Juan Del Valle, Ph.D.
anticancer, antivirus, multiple myeloma, peptide, Peptidomimetics
The high demand of novel peptide and peptidomimetics based on the amount of
genomic and proteomic data need be matched by synthesis and screening. The design and
synthesis of peptide and peptidomimetics are so important because the peptide and
protein-protein interaction play a key role in molecule recognition and signaling. The
modified peptides have better stability and pharmacokinetic properties which may be guided
by rational design and molecular modeling. Now many organic and medicinal chemists have
chosen peptide and peptidomimetics as potential drug candidates for many targets.
In this dissertation, research efforts in design and synthesis of cyclic peptides with
stabilized secondary structure have been investigated. Cyclization of linear peptides may
restrict the number of available conformations which may improve the affinity attaching to
the target. In this study, different beta turn linkers have been designed and synthesized to
achieve more stable cyclic peptides with beta-sheet structures. Based on different beta turn
linkers, analogs of cyclic peptides have been synthesized and screened. The structure activity
relationships (SAR) of these cyclic peptide analogs have been studied.
In chapter three, analogs of peptidomimetic inhibitors have been designed and
synthesized. These peptide analogs are targetingHuman Rhinovirus (HRV) and Coronavirus
(CoV) by inhibiting the cysteine protease. The docking and modeling studies have been
shown. The structures of this kind of inhibitors include five fragments. The warhead provides
the activity, which can covalently react with the thiol of cysteine protease and permanently
eliminate its proteolytic activity. The warhead is linked to a peptide backbone including the
other four parts that are designed to position the warhead where it can specially react with the
critical thiol of the cysteine protease active site. The side chain of each amino acid has been
optimized to achieve better solubility and permeability. We successfully synthesized some
compounds with good potency.
Scholar Commons Citation
Liang, Yi, "Design, Synthesis and Screening of Some Anticancer/Antiviral Drug Candidates" (2016). Graduate Theses and Dissertations.