科研之友
微信
新浪微博
Facebook
分享链接
摘要
A model for predicting the slope (S) in the fundamental equation of linear-solvent-strength theory for peptidic compounds was developed. Our approach is based on the novel assumption that three well-defined molecular descriptors: peptide length (N), charge (Z) and hydrophobicity index (HI) are the major contributors to the value of S. Following the definition of the model's variables, the retention of a number of Arg-terminated synthetic peptides was investigated under isocratic elution conditions (100 A pore size C18 phase, 0.1% trifluoroacetic acid as ion-pairing modifier). The peptide sequences were systematically designed to span the properties of the typical tryptic peptides that are analyzed in proteomic experiments. Experimental data show that slopes S increase with the independent increase in both peptide charge and peptide length when the two other parameters are held constant. The influence of peptide hydrophobicity is more complex: depending on peptide length and charge, stronger RP-HPLC retention can either decrease or increase the values of S. We postulate a general function to explain this behavior: S=C1 x Z(C2) + C3 x N(C4) + C5 x Hl(C6) + C7/Z+ C8/N + C9/HI+ C10 x ZN + C11 x ZHI + C12 x NHI+ B. A simple optimization using a "random walk" through parameter-space was used to determine the optimal coefficients compared to the measured S-values of 37 peptides. The model gives a similar to 0.97 R(2) correlation between the measured and predicted S-values: it was verified against previously published data on a human growth hormone protein tryptic digest and some synthetic analogues from that mixture.
- 出版日期2010-1-22
