Stereochemical Requirements for -Hairpin Formation: Model Studies with Four-Residue Peptides and Depsipeptides
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- 作者：Tasir S. Haque ; Jennifer C. Little ; and Samuel H. Gellman
- 刊名：Journal of the American Chemical Society
- 出版年：1996
- 出版时间：July 24, 1996
- 年：1996
- 卷：118
- 期：29
- 页码：6975 - 6985
- 全文大小：894K
- 年卷期：v.118,no.29(July 24, 1996)
- ISSN：1520-5126
文摘
Spectroscopic and crystallographic data are presentedfor a series of tetrapeptides and analogousdepsipeptides that can form a minimal 
-hairpin (two intramolecularhydrogen bonds). These model compoundshave been used to test the hypothesis that "mirror image" -turnspromote -hairpin formation. This hypothesis wasinspired by a statistical survey of -hairpins in globular proteins(Sibanda, B. L.; Thornton, J. M. Nature 1985,316,170), which showed that mirror image -turns (type I' and type II'),although rare in general, are very commonlyassociated with -hairpins containing a two-residue loop between thestrand segments. Each of our four-residuemolecules contains proline at the second position, to promote a central-turn. The -turn is induced to be either"common" or "mirror-image", relative to the outer residues, bychoice of residue configuration (L vs D).In methylenechloride, end-capped tetrapeptideAc-L-Val-D-Pro-D-Ala-L-Leu-NMe2folds largely into the -hairpin conformation,while the diastereomerAc-L-Val-L-Pro-L-Ala-L-Leu-NMe2displays little or no -hairpin folding. For eachdiastereomer, the hydrogen-bonded driving force for -hairpin foldingis identical, and the dramatic difference infolding behavior therefore reflects a variation in the intrinsicconformational properties of the diastereomeric backbones.Similar behavior is seen for the diastereomeric peptide pairAc-L-Val-D-Pro-Gly-L-Leu-NMe2vs Ac-L-Val-L-Pro-Gly-L-Leu-NMe2, and for the analogousdepsipeptides with a lactic acid or glycolic acid residue at the thirdposition.Thus, our results show not only that mirror-image Pro-X turnsstrongly promote -hairpin folding, but also thatcommon -turns strongly discourage formation of a -hairpin with atwo-residue loop.
-hairpin (two intramolecularhydrogen bonds). These model compoundshave been used to test the hypothesis that "mirror image" -turnspromote -hairpin formation. This hypothesis wasinspired by a statistical survey of -hairpins in globular proteins(Sibanda, B. L.; Thornton, J. M. Nature 1985,316,170), which showed that mirror image -turns (type I' and type II'),although rare in general, are very commonlyassociated with -hairpins containing a two-residue loop between thestrand segments. Each of our four-residuemolecules contains proline at the second position, to promote a central-turn. The -turn is induced to be either"common" or "mirror-image", relative to the outer residues, bychoice of residue configuration (L vs D).In methylenechloride, end-capped tetrapeptideAc-L-Val-D-Pro-D-Ala-L-Leu-NMe2folds largely into the -hairpin conformation,while the diastereomerAc-L-Val-L-Pro-L-Ala-L-Leu-NMe2displays little or no -hairpin folding. For eachdiastereomer, the hydrogen-bonded driving force for -hairpin foldingis identical, and the dramatic difference infolding behavior therefore reflects a variation in the intrinsicconformational properties of the diastereomeric backbones.Similar behavior is seen for the diastereomeric peptide pairAc-L-Val-D-Pro-Gly-L-Leu-NMe2vs Ac-L-Val-L-Pro-Gly-L-Leu-NMe2, and for the analogousdepsipeptides with a lactic acid or glycolic acid residue at the thirdposition.Thus, our results show not only that mirror-image Pro-X turnsstrongly promote -hairpin folding, but also thatcommon -turns strongly discourage formation of a -hairpin with atwo-residue loop.