Bodzioch K, Baczek T, Kaliszan R, Vander Heyden Y
Department of Analytical Chemistry and Pharmaceutical Technology, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, 1090 Brussels, Belgium.
J Pharm Biomed Anal. 2009 Nov 1;50(4):563-9. doi: 10.1016/j.jpba.2008.09.004. Epub 2008 Sep 9.
The use of the experimental molecular descriptor logSum(AA) and some possible alternatives were evaluated in the QSRR analysis of peptides. To quantitatively characterize the structure of analytes in a previously proposed QSRR the following three structural descriptors were applied: the logarithm of the sum of gradient retention times of the amino acids composing the individual peptide, logSum(AA); the logarithm of the peptide's van der Waals volume, logVDW(Vol); and the logarithm of its theoretically calculated n-octanol-water partition coefficient, clogP. Taking into consideration that most amino acids were hardly retained in the different RP-HPLC systems on which the peptides retention was measured, the contribution of most amino acids to the logSum(AA) descriptor is rather constant. Therefore, to enlarge the variability of the descriptor and the amino acids contributions for a given series of peptides, in a first instance, it was evaluated whether, by changing the chromatographic conditions, the retention differences between the amino acids could be increased, while maintaining their mutual selectivity. It was not evident to find such conditions. Secondly, it was also investigated whether the experimental descriptor logSum(AA) can be replaced by a theoretical, either based on a simple or on a weighted counting of the amino acids composing the peptide. The weighting factor for the retained amino acids was determined by their experimental gradient retention times measured on different systems. The predictive abilities of the new QSRR models (applying the alternative descriptors) were assessed using the leave-one-out cross-validation procedure and compared to that of the initial model. Finally, a descriptor was defined for which the retention measurement of only a limited number of amino acids is required. It resulted in QSRR models with similar predictive properties as those with logSum(AA), but with a reduced workload.
在肽的定量结构-保留关系（QSRR）分析中，对实验性分子描述符logSum(AA)及其一些可能的替代方法进行了评估。为了在先前提出的QSRR中定量表征分析物的结构，应用了以下三个结构描述符：组成单个肽的氨基酸梯度保留时间总和的对数，logSum(AA)；肽的范德华体积的对数，logVDW(Vol)；以及其理论计算的正辛醇-水分配系数的对数，clogP。考虑到大多数氨基酸在测量肽保留的不同反相高效液相色谱（RP-HPLC）系统中几乎不保留，大多数氨基酸对logSum(AA)描述符的贡献相当恒定。因此，为了扩大给定肽系列中描述符的变异性和氨基酸贡献，首先评估了通过改变色谱条件，在保持氨基酸相互选择性的同时，是否可以增加氨基酸之间的保留差异。找到这样的条件并不明显。其次，还研究了实验描述符logSum(AA)是否可以被基于组成肽的氨基酸的简单计数或加权计数的理论描述符所取代。保留氨基酸的加权因子由它们在不同系统上测量的实验梯度保留时间确定。使用留一法交叉验证程序评估了新的QSRR模型（应用替代描述符）的预测能力，并与初始模型进行了比较。最后，定义了一个描述符，对于该描述符，只需要测量有限数量氨基酸的保留情况。结果得到的QSRR模型具有与使用logSum(AA)的模型相似的预测特性，但工作量减少。
