The effect of a trans-locked Gly-Pro alkene isostere on collagen triple helix stability
The effect of a trans-locked Gly-Pro alkene isostere on collagen triple helix stability
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DOI：
10.1021/ja711021m
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发表时间：
2008-04-23
影响因子：
15
通讯作者：
Etzkorn, Felicia A.
中科院分区：
文献类型：
--
作者：
Dai, Nan;Wang, Xiaodong J.;Etzkorn, Felicia A.
合成了甘氨酸-反式-Pro的烯烃异构体，并将其引入到宿主Ac-(Gly-Pro-Hyp)(8)-Gly-GlyTyr-NH2多肽中，研究了其对脯氨酸酰胺键的锁定作用。脯氨酸酰胺键异构化是胶原蛋白折叠过程中的缓慢步骤。通过锁定酰胺，我们假设胶原三螺旋的稳定性增加。取而代之的是破坏了胶原蛋白主肽的稳定性。宿主控制肽的T-m值为50.0℃，而包含同功酶的多肽Ac-(Gly-Pro-Hyp)(3)-Gly-psi[(E)CH=C]-Pro-Hyp-(Gly-Pro-HyP)(4)-Gly-Gly-Tyr-NH2，的T-m值为28.3℃。显然，影响胶原稳定性和折叠的因素尚不清楚。
An alkene isostere of Gly-trans-Pro was synthesized and incorporated into a host Ac-(Gly-Pro-Hyp)(8)-Gly-GlyTyr-NH2 peptide to investigate the effect of locking a proline amide bond. Proline amide bond isomerization is the slow step in collagen folding. By locking the amide, we hypothesized an increase in stability of the collagen triple helix. The substitution instead destabilized the collagen host peptide. The T-m value of the host control peptide was 50.0 degrees C, while the peptide containing the isostere,Ac-(Gly-Pro-Hyp)(3)-Gly-psi[(E)CH=C]-Pro-Hyp-(Gly-Pro-HyP)(4)-Gly-Gly-Tyr-NH2, had a T-m value of 28.3 degrees C. There are clearly factors that contribute to Collagen stability and folding that we do not yet understand.