טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentBaskin Maria
SubjectPeptoid Oligomers as Unique Chelators for Metal Ions
towards Biomimetic Applications
DepartmentDepartment of Chemistry
Supervisor Professor Galia Maayan
Full Thesis textFull thesis text - English Version


Abstract

Metal ions play a significant role in the activity of biological systems including catalysis, recognition and protein folding. The significance of metal ions in nature is expressed in their vast presence within biopolymers. Therefore, introducing metal ions into biomimetic oligomers is a potential way for creating artificial structures towards the design and production of effective functional materials. Yet, the key for generating functional metallo-biomimetic materials lays in understanding the interactions between the organic environment represented by the synthetic oligomers and biologically relevant metal ions. The objective of this research is to gain new insights regarding the interactions between metal ions and peptoids, N-substituted glycine oligomers, as tools for structural studies and biomimetic applications. Peptoids are a family of peptidomimetic foldamers capable of adopting stable secondary structures in solution if chiral bulky groups are incorporated within the peptoid sequence. Thus, helical secondary structure of peptoids is forced due to local steric and stereoelectronic interactions and mostly resembles that of the polyproline-type I helix, with a pitch of three residues per turn. Peptoids are synthesized efficiently using the solid phase submonomer method which enables facile incorporation of a wide variety of side chains resulting in high diversity of the peptoid sequence.  The ease of peptoid synthesis and their versatile backbone as well as their stability and biocompatibility make them excellent candidates for exploring the interactions between metal ions and peptidomimetics. This work includes rational design, synthesis and characterization of unique metal-binding peptoids for biomimetic applications. Tuning the peptoids sequence and length as well as their chemical properties will enable the formation of unique metal-peptoid complexes towards applications such as folding, selective recognition, chiral induction and cooperativity. In terms of folding, we show for the first time that designed unstructured peptoids can fold upon metal binding to form helical structures. In addition, we demonstrate the development, by rational design, of metallopeptoids as functional materials including highly selective chelators for different metal ions in various recognition processes as well as for allosteric cooperativity and chiral induction from the peptoid oligomers to the metal centers.