טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAlisa Smolyakova
SubjectPeptide Mimics by Design: Structural Control via
Sequence Modification
DepartmentDepartment of Chemistry
Supervisor Dr. Maayan Galia
Full Thesis textFull thesis text - English Version


Abstract

Peptoids - oligomers of N-substituted glycine are a type of biotic foldamers that can fold into well-defined secondary structures in solution. Peptoids are incapable to form hydrogen bonds thus their helical structures are similar to polyproline type helices (PP-I and PP-II) with a pitch of about 3 residues per turn. Controlling the secondary structure of peptoids as well as controlling structures of other molecules by peptoid sequences might lead to the creation of interesting function. Thus this thesis includes two projects: the first one is focused on controlling helix stability via metal coordination and the second is focused on controlling zeolites growth by modified peptoid sequences. The latter was done in collaboration with Prof. Rimer’s group from the University of Houston, USA. The creation of folded structures in heterooligomers requires the use of at least 66% chiral bulky side groups in the sequence, thus restraining the design of folded peptoids and limiting their properties and applications. Herein we explored the use of 8-hydroxyquinoline (HQ) ligands at positions 2 and 5 (i and i) along three different peptoid heptamer backbones that are composed of chiral (S)-1-phenylethyl (Nspe) and (S)-1-methoxy-2-propyl (Nsmp) side groups in order to investigate conformational changes in peptoids induced by metal coordination. We have found that the positions of the bulky aromatic residues (Nspe groups) have strong effect on the secondary structure of the metallopeptoids and on their ability to bind metal ions: a peptoid with a bulky core (2 Nspe groups at positions 3 and 4) can adopt well-defined secondary structure upon Cu(II) and Zn(II) binding and have a high affinity to these ions. In addition, we exploited peptoids as zeolite growth modifiers and study the influence of various peptoid sequences on the kinetic of zeolite growth and morphology. As the high density of hydroxyl groups (SiOH, AlOH) in the 001 direction, the binding of growth modifiers to zeolites surfaces requires the use of hydrogen-binding moieties. Thus, we have used primary amines and alcohols as binding groups and methoxyethyl and benzyl N-substituted groups as spacer agents to construct 16 peptoid sequences and tested them in zeolilte synthesis. We have found that peptoids are good growth modifiers, having a stronger effect on the kinetics of zeolite growth than on the morphology of zeolite crystals. Thus, studies on kinetic inhibition of zeolite growth by peptoids we showed that the amine containing peptoids have a superior effect on kinetic inhibition than alcohols containing peptoids. All peptoids sequences were synthesized either by the “sub-monomer” method on solid support or in solution phase, cleaved, purified, analyzed by HPLC and ESI-MS and characterized by UV-Vis, FTIR, NMR, EPR and CD spectroscopies.