The Effect Of N-?* Hyper-conjugation Interactions On Conformation Of P_? In Model Peptides

The protein folding problem remains one of the most challenging problems in the field of biophysics.Protein is one of the important components of living cells,it plays various crucial roles in many biological processes including growth?development and metabolism.Protein exists mainly in two states in aqueous solution,the initial state?unfold state?and the final state?folding state?.Previous studies indicate that short model peptides exist mainly in P_?I conformation in aqueous solution,it is likely that proteins in unfolded states also exist in P_?I conformation.P_?I conformation stability is controlled by different forces:main chain side chain interaction,dipole-dipole interaction,solvation effects and n-?*hyper-conjugation interactions may play important roles for the P_?I conformation stability.This thesis mainly studies n-?* hyper-conjugation interactions and their effects on the distribution of P_?I conformation in short model peptides.Raines group studied the n-?*hyper-conjugation interactons by focusing on proline derivatives:proline derivativeshaveshown a equlibriumof cisandtrans conformations:n-?*hyper-conjugation interactions existing only in trans form.The inductive electronic effect and steric effect are expected to interfere with the n-?*hyper-conjugation interactions,thus the contents of trans form and the Ktrans/cis value change accordingly.Ktrans/cis measures the strength of the n-?*hyper-conjugation interations.We have designed two series of short model peptides:X-CO-aa-OMe and X-CO-Leu-COOH?aa=Ala,Val,Leu,Ile,Phe,Pro;X=Me₂CH,Me₃C,F₃C,ClCH₂,Cl₂CH,Cl₃C?.Upon varying steric effect of substitute X,it is expected that the strength of n-?*hyper-conjugation interations change accordingly.The trans/cis ratio of proline derivative can be measured by¹H NMR,the P_?I contents of the non-priline amino acid derivatives can be calculated from the measured ³J_?N.P_?I conformation can be firmed by circular dichroism spectrum.Our experimental date indicates that the effects of the n-?*hyper-conjugation interations on the stability of P_?:both the electronic inductive effect and the steric effect can interfere with the n-?*hyper-conjugation interations.From our previous studies,a electron-withdrawing substitution enhances the n-?*interations,the content of P_?I conformation increases accordingly.This study indicates that the n-?*interations are intensifired by a stronger steric effect,the content of P_?I in non-proline amide acid derivates increase accordingly.Our data show that the n-?*interations contribute to the stability of P_?.Our data show that the polarity of solvents has some effects on n-?* interations.