Energetic Contribution Of N-π~*Hyperconjugation Interations To Short Model Peptides’ PolyprolineⅡ Conformations

Protein molecules exist in aqueous solution in two-state equilibrium: the initial state(unfolded state) and the final state (folded state). Recent study showed that short modelpeptides exist mainly in PPⅡconformation in aqueous solution, suggesting protein inaqueous solution may be domained by PPⅡconformation as well. Why PPⅡin unfoldedstates of proteins? A variety of non-covalent interactions such as solvation effects, stericeffects, backbone-side chain interactions, dipole-dipole interactions and n-π*hyper-conjugation interactions may play important roles in stabilizing PPⅡconformationsin unfolded states of proteins.In this thesis, we focus on n-π*hyper-conjugation interactions and their effects onshort model peptides; and how n-π*hyper-conjugation interactions change with solventsof different polarity. Raines group has investigated n-π*hyper-conjugation interactions bystudying proline derivaties. There are cis and trans isomers in proline peptides and n-π*hyper-conjugation interactions exist only in trans conformation. As a result, Ktrans/cisofproline derivaties can report the strength of n-π*interactions.We have designed two series of short model peptides: p-X-C6H4-aa-OMe andAc-aa-NH-C6H4-p-X（aa=Ala，Val，Phe，Leu，Ile，Pro；X=OMe，Me，H，Cl，NO2）. Upon varying electronic withdrawing capability of substitute X, it is expected thatthe strength of n-π*hyper-conjugation interactions change accordingly. The trans/cis ratioof proline derivative can be measured by1H NMR; PPⅡcontents and ΔG values fornon-proline amino acid derivatives can be calculated from measured3JNvalues. Possibleconnection between PPⅡcontents and the strength of n-π*hyper-conjugation interactionsas derived from trans/cis ratios will be examined to find out if n-π*interactions favor PPⅡ.Our date indicate that n-π*interactions become stronger with a moreelectron-withdrawing substitute group, PPII contents increase with the strength of n-π*interactions and a linear correlation between ΔG and the Hammett parameter σpof the substitute is revealed. The results show that the n-π*interactions can stabilize the PPIIconformation. In solvents with different polarity, the slopes of the correlation between ΔGand the Hammett parameter σpare essentially the same, which implies that the strength ofn-π*hyper-conjugation interactions will not change with the polarity of the solvent.