ESTIMATE OF BARRIERS HINDERING ROTATION ABOUT CALPHA-C' BOND BETWEEN CIS' AND TRANS' CONFORMATIONS IN AN ISOLATED L-PROLINE RESIDUE
ESTIMATE OF BARRIERS HINDERING ROTATION ABOUT CALPHA-C' BOND BETWEEN CIS' AND TRANS' CONFORMATIONS IN AN ISOLATED L-PROLINE RESIDUE
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DOI：
10.1021/ja00799a020
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发表时间：
1973-01-01
影响因子：
15
通讯作者：
TONELLI, AE
中科院分区：
文献类型：
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作者：
TONELLI, AE
本文用半经验势函数估算了L-脯氨酸反式肽键中顺式（~125）和反式（~325）最低能量构象绕C "-C"键转动的势垒。非键排斥和伦敦色散相互作用用6 - 12位势计算，静电相互作用则用C-S近似处理。Brant的方法解释了吡咯烷环前面的羰基氧和后面的酰胺质子之间的氢键作用。此外，价角畸变和肽键旋转导致的非平面构象被认为是。所有的键长都是固定的，而价角和旋转角，，和是变化的。发现在ε = 60和210处计算的顺式和反式构象之间的势垒显著低于顺式-反式势垒（oz. 20 kcal/mol）。事实上，这两个势垒都小于10 kcal/mol，在室温下不会导致单独的核磁共振（一个是顺式，另一个是反式）。价角偏离其结晶值，这极大地减轻了吡咯烷环之后的脯氨酸羰基和NH基团与吡咯烷环的β-CH 2基团以及与吡咯烷环之前的羰基之间的空间相互作用，并且当~210时，吡咯烷环之前的羰基和之后的NH基团之间的分子内氢键，如前所述，考虑到小障碍。在使用核磁共振光谱（nmr）和构象能估计确定含有分离的L-脯氨酸残基（一个L-脯氨酸残基没有被另一个脯氨酸残基取代13）的几种环肽（合成的1 - 6和生物活性的7 - 11）的溶液构象的过程1 - 12中，关于C "-C '键的旋转障碍的大小的问题（参见
The barriersto rotation about the C “-C'bond between the cis'(~ 125) and trans'(~ 325) minimum energy conformations in an isolated trans peptide bond L-proline residue are estimated using semiempirical potential functions. Nonbonded repulsiveand London dispersion interactions are evaluated using a 6-12 poten-tial, whileelectrostatic interactions are treated in the monopole-monopole approximation. Contributions made by hydrogen bonding between the carbonyl oxygen preceding and the amide proton succeeding the pyrrolidine ring are accounted for by the method of Brant. In addition, valence angle distortion and peptide bond rotation resulting in nonplanar conformations are considered. All bond lengths are fixed, while the valence angles and the angles of rotation,, and are varied. The calculated barriers at^= 60 and 210 between the cis' and trans' conformations are found to be significantly lower than the cis-trans barrier (oz. 20 kcal/mol) about the peptide bond. In fact, both barriers are less than 10 kcal/mol and would not lead to separate nuclear magnetic resonances (one for cis' and another for trans') at room temperature. Distortion of the valence angles from their crystalline values, which greatly relieve the steric interactions of the proline carbonyl group and the NH group succeeding the pyrrolidine ring with the/3-CH2 group of the pyrrolidine ring and with the carbonyl group preceding the pyrrolidine ring, and when~ 210, the intramolecular hydrogen bond between the carbonyl group preceding and the NH group succeeding the pyrrolidine ring, as suggested previously, account for the small barriers. uring the course1-12 of determining the solution conformations of several cyclic peptides (synthetic1-6 and biologically active7-11) containing isolated L-proline residues (an L-proline residue not suc-ceeded by another proline residue13) using nuclear magnetic resonance spectroscopy (nmr) and confor-mational energy estimates, the question of the magnitude of the barrier to rotation about the C “-C'bond (see