Protein retention, predictability

Hallgren, E., Prediction of protein retention at gradient elution conditions in ion-exchange chromatography, /. Chromatogr. A, 852, 351, 1999. 

Numerous researchers have dedicated their efforts to understanding the relationship between peptide and protein molecular properties (molecular mass and charge, hydrophobicity, surface charge anisotropy, surface area) and their retention in CEC as a function of field strength, gradient steepness, temperature, and variables related to surface characteristics of the stationary phase. So far, however, no reliable and comprehensive theory is available to model and predict peptide and protein retention, and the need to interface CEC with mass spec-... 

C. B. Mazza, N. Sukumar, C. M. Breneman and S. M. Cramer, Prediction of protein retention in ion-exchange systems using molecular descriptors obtained from crystal structure.. Anal. Chem., 2001, 73, 5457-5461. 

M. Song, C. M. Breneman, J. Bi, N. Sukumar, K. P. Bennett, S. Cramer and N. Tugcu, Prediction of protein retention times in anion-exchange chromatography systems using support vector regression., J. Chem. Inf. Comput. Sci., 2002, 42, 1347-1357. 

Tugcu, N., Song, M., Breneman, C.M., Sukumar, N., Bennett, K.P. and Cramer, S.M. (2003) Prediction of the effect of mobile-phase salt type on protein retention and selectivity in anion exchange systems. Anal. Chem., 75, 3563-3572. 

Ijalsma, H. and van Dijl, J.M. (2005) Proteomics-based consensus prediction of protein retention in a bacterial membrane. Proteomics,... 

The model can also be used to predict animal performance. For example, if the NE intake of the pig was restricted to 20.0 MJ/day and the predicted rate of protein retention is 0.172 kg/day, the rate of lipid retention can be predicted as follows ... 

Mahn A, Asenjo JA. Prediction of protein retention in hydrophobic interaction chromatography. Biotech Ad 2005 23(5) 359—68. 

Retention in HIC can be described in terms of the solvophobic theory, in which the change in free energy on protein binding to the stationary phase with the salt concentration in the mobile phase is determined mainly by the contact surface area between the protein and stationary phase and the nature of the salt as measured by its propensity to increase the surface tension of aqueous solutions [331,333-338]. In simple terms the solvopbobic theory predicts that the log u ithn of the capacity factor should be linearly dependent on the surface tension of the mobile phase, which in turn, is a llne2u function of the salt concentration. At sufficiently high salt concentration the electrostatic contribution to retention can be considered constant, and in the absence of specific salt-protein interactions, log k should depend linearly on salt concentration as described by equation (4.21)... 

Sasagawa, T. and Teller, D. C., Prediction of peptide retention times in re-versed-pahase HPLC, in CRC Handbook of HPLC for the Separation of Amino Acids, Peptides, and Proteins, Vol. II, Hancock, W. S., Ed., CRC Press, Boca Raton, FL, 1984, 53. 

There have been several reports where plasma protein binding data was used in the prediction of in vivo properties of compounds. Two papers noted that the ability to predict in vivo clearance from in vitro microsome data was greatly improved when a plasma protein binding term was included [64,65]. In another study, binding to phospholipids and human serum albumin was assessed by HPLC retention times (on IAM and HAS columns, respectively) and used to predict volume of distribution [66]. 

Figure 4.1 Correlation of predicted and observed retention times in reversed-phase chromatography. The predicted retention times for 58 peptides of 2 to 16 residues in length were obtained by summation of retention coefficients for each residue in the peptide. Retention coefficients were determined from the retention of model synthetic peptides with the structure Ac-Gly-XX-(Leu)3-(Lys)2-amide, where X was substituted by the 20 protein amino acids. (Reproduced from D. Guo, C.T. Mant, A.K. Taneja, and R.S. Hodges, J. Chromatogr., 359 519 [1986]. With permission from Elsevier Science.)...

Differential hydration of proteins has been little exploited as a selectivity factor in ion exchange, but it is simple to evaluate and can produce useful results. This technique relies on the preferential exclusion of certain solutes from protein surfaces to produce an exclusionary effect and favor their interaction with the column. Protein hydration is generally proportional to protein size and solubility. Among proteins of similar size, this predicts that retention will increase with protein solubility. Among proteins of similar solubility, retention increases with protein size.16... 

The usefulness of protein-type CSPs has already been shown in particular Chiral-AOP and Ultron ES-OVM (see Table 2) have a very broad range of enantioselectivity. It is not, however, possible to systematically predict the resolution on such CSPs, but the overall retention, selectivity and efficiency can be modified to a certain extent by altering several key variables ... 

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