The solution conformation of Ac-Pen-Arg-Gly-Asp-Cys-OH, a potent fibrinogen receptor antagonist, was characterized in DMSO-d6 by the combination of nmr and molecular modeling. The conformational space available to the peptide was explored using a distance geometry algorithm with distance constraints derived from 1H-nmr spectra. The dynamics of the peptide were examined by relaxation time measurements and low temperature studies. The results from the low temperature studies suggest that the peptide backbone does not exist in a single, well-defined conformation but undergoes exchange between multiple conformers. This result is consistent with the inability to find a single structure that satisfies all the nmr-derived constraints. The constraints could only be satisfied by considering pairs of conformers to represent the experimental data. The low energy conformers comprise type II' or type V beta-turns with distinct side-chain directionality. The Arg-Gly-Asp portion of the ring is flexible and can be described by amide-plane rotations of the Arg-Gly and Gly-Asp peptide bonds. Although some backbone flexibility is evident, the incorporation of beta,beta-dimethyl cysteine imparted greater conformational rigidity as compared to the previously studied cyclic pentapeptide, Ac-Cys-Arg-Gly-Asp-Cys-OH.

中文翻译：

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Ac-Pen-Arg-Gly-Asp-Cys-OH（一种有效的纤维蛋白原受体拮抗剂）的溶液构象。

有效的纤维蛋白原受体拮抗剂Ac-Pen-Arg-Gly-Asp-Cys-OH的溶液构象在DMSO-d6中通过nmr和分子建模相结合进行了表征。使用具有1H-nmr光谱的距离约束的距离几何算法探索了肽可用的构象空间。通过弛豫时间测量和低温研究检查了肽的动力学。低温研究的结果表明，肽主链不存在于一个单一的，明确定义的构象中，而是在多个构象子之间进行交换。此结果与无法找到满足所有nmr派生的约束的单个结构相一致。只能通过考虑成对的构象异构体来表示实验数据来满足约束条件。低能构象异构体包含具有明显侧链方向性的II'型或V型β-转角。环的Arg-Gly-Asp部分是柔性的，可以通过Arg-Gly和Gly-Asp肽键的酰胺平面旋转来描述。尽管一些骨架柔性是明显的，但是与先前研究的环状五肽Ac-Cys-Arg-Gly-Asp-Cys-OH相比，β，β-二甲基半胱氨酸的引入赋予更大的构象刚度。