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Peptides of Alpha-Aminoxy acids : novel secondary structures and applications as selective chloride receptors

by Li, Wei

Abstract (Summary)
(Uncorrected OCR) Abstract of thesis entitled PEPTIDES OF ALPHA-AMINOXY ACIDS: NOVEL SECONDARY STRUCTURES AND APPLICATIONS AS SELECTIVE CHLORIDE RECEPTORS Submitted by Li Wei for the Degree of Doctor of Philosophy at The University of Hong Kong in August 2004 'Foldamers' are sequence-specific oligomers that can adopt various well-defined secondary structures, such as helices, turns and sheets. Great progress has recently been made in this field to mimic natural peptides or proteins with specific biological activities. As one of the types of building blocks of foldamers, a-aminoxy acid was found to induce a chiral N-0 turn with an eight-membered-ring intramolecular hydrogen bond between adjacent residues. In this project, conformational studies, possible applications, as well as the solid-phase synthesis of oligomers containing a-aminoxy acids have been carried out and the main results are summarized below. H NMR and IR studies on the oligomers of alternating a-aminoxy acids and a-amino acids suggest that peptides 1-5 as well as 16-20 could form eight-membered-ring intramolecular hydrogen bonds (N-0 turns) and seven-membered ring intramolecular hydrogen bonds (y-turns) simultaneously. Furthermore, 2D NMR, CD spectroscopy and theoretical calculations have revealed that hetero-chiral peptides 1-5 adopt a mixed 7/8 helical conformation, whereas the homo-chiral ones 16-20 form a reverse turn structure in non-polar solvents as well as in a polar solvent, methanol. Short linear peptides 28, 33, 35 and 40 containing a-D,L-aminoxy dipeptide segments have been found to bind anions such as chloride and bromide ions in a 1:1 ratio. The association constants determined by NMR titrations indicate that, among those peptides, 40 has the highest affinity for CT (7587 MT1) with good selectivity (3.5 folds over Br-). Further investigations on peptide 41, which has even larger binding affinity to Cl~ (Ka > 105 M-1), suggest that conformationally rigid reverse turn structure is not a prerequisite for anion binding. The solid-phase synthesis strategy has been applied to the preparations of a-aminoxy peptides 50, 55 and 58. PS-1%DVB Wang resin was used as a solid support. HBTU/HOBt/DIPEA and benzoyl chloride were employed as the coupling and capping reagents, respectively. The JV-deprotection was performed in 5 % NH2NH2H2O in MeOH for a total 9 h, and 50 % TFA in CH2CI2 were utilized to cleave the peptides from the resin. The tetrapeptide 55 and tripeptide 58 were prepared via this solid-phase synthesis strategy in 54 % and 72 % overall yields, respectively. j^&x YfVfcVr V^ o o 1 Ha f Hb N ?fYiVr o o * Ho Jk. Hd o o Ha Y Hb o o 16 g z Hb ? Hc II II i: Hc ? Hd 17 18 0 z /\ ? ? \^ 19 O O = /^ O O k^J 20 Ph Ha Hjj I Hc N VvN V- -N Hb 1 Ha Ha ( Hb H0 ; Hb I Ha ___ Ha ~. Hb I H0 O O O O 0 O 35 ^ Hb I H l o Yd o H -N. O O OH n-o^y^o^y^o-^y0" 0 0 0 50 58
Bibliographical Information:

Advisor:

School:The University of Hong Kong

School Location:China - Hong Kong SAR

Source Type:Master's Thesis

Keywords:peptides synthesis oligomers anions

ISBN:

Date of Publication:01/01/2005

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