Determination of solute descriptors of tripeptide derivatives based on high-throughput gradient high-performance liquid chromatography retention data

Plass, Monika; Valkó, Klára; Abraham, Michael H.

doi:10.1016/s0021-9673(97)01215-6

Cited by 44 publications

(24 citation statements)

References 32 publications

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“…The coefficients in eq 6 are found by multiple linear regression analysis, using a set of solutes for which the descriptors are known. There are numerous applications of eq 6 to physicochemical properties, both by ourselves [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] and by other workers, [48][49][50][51][52][53][54][55][56][57][58][59] so that eq 6 can be regarded as a well-established general equation. Tables 2 and 3 in ref 7.…”

Section: Methodsmentioning

confidence: 99%

The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship

Abraham

1999

Journal of Pharmaceutical Sciences

297

162

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The aqueous solubility of liquids and solids, as log S(W), has been correlated with an amended solvation equation that incorporates a term in Sigma alpha(2)(H) x Sigma beta(2)(H), where the latter are the hydrogen bond acidity and basicity of the solutes, respectively. Application to a training set of 594 compounds led to a correlation equation with a standard deviation, SD, of 0.56 log units. For a test set of 65 compounds, the SD was 0.50 log units, and for a combined correlation equation for 659 compounds, the SD was 0.56 log units. The correlation equations enable the factors that influence aqueous solubility to be revealed. The hydrogen-bond propensity of a compound always leads to an increase in solubility, even though the Sigma alpha(2)(H) x Sigma beta(2)(H) term opposes solubility due to interactions in the liquid or solid. Increase in solute dipolarity/polarizability increases solubility, whereas an increase in solute excess molar refraction, and especially, volume decrease solubility. The solubility of Bronsted acids and bases is discussed, and corrections for the fraction of neutral species in the saturated solution are graphically presented.

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Section: Methodsmentioning

confidence: 99%

The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship

Abraham

1999

Journal of Pharmaceutical Sciences

297

162

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“…RP-HPLC has frequently been employed to generate amino acid side-chain hydrophilicity/hydrophobicity scales (or "coefficients") from peptides [2]. Initially, this approach involved assignment of hydrophilicity/hydrophobicity values of amino acid sidechains through regression analysis of the RP-HPLC retention times of a random collection of peptides of varied composition and length [3][4][5][6][7][8][9][10][11][12]. More recent work has included a quantitative structure-retention relationship (QSRR) approach, taking into account additional factors (peptide Van der Waals volume, theoretical n-octanol/water partition coefficient) to that of overall peptide hydrophobicity (as expressed by RP-HPLC retention time), albeit this predictive model still relies on multiple regression analysis of random peptides [13,14].…”

Section: (I) Amino Acid Compositionmentioning

confidence: 99%

Requirements for prediction of peptide retention time in reversed-phase high-performance liquid chromatography: Hydrophilicity/hydrophobicity of side-chains at the N- and C-termini of peptides are dramatically affected by the end-groups and location

Tripet

Cepeniene

Kovacs

et al. 2007

Journal of Chromatography A

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The value of reversed-phase high-performance liquid chromatography (RP-HPLC) and the field of proteomics would be greatly enhanced by accurate prediction of retention times of peptides of known composition. The present study investigates the hydrophilicity/hydrophobicity of amino acid sidechains at the N-and C-termini of peptides while varying the functional end-groups at the termini. We substituted all 20 naturally occurring amino acids at the N-and C-termini of a model peptide sequence, where the functional end-groups were N α -acetyl-X-and N α -amino-X-at the N-terminus and -X-C α -carboxyl and -X-C α -amide at the C-terminus. Amino acid coefficients were subsequently derived from the RP-HPLC retention behaviour of these peptides and compared to each other as well as to coefficients determined in the centre of the peptide chain (internal coefficients). Coefficients generated from residues substituted at the C-terminus differed most (> 2.5 min between the -X-C α -carboxyl and -X-C α -amide peptide series) for hydrophobic side-chains. A similar result was seen for the N α -acetyl-X-and N α -amino-X-peptide series, where the largest differences in coefficient values (> 2 min) were observed for hydrophobic peptides. Coefficients derived from substitutions at the Cterminus for hydrophobic amino acids were dramatically different compared to internal coefficients for hydrophobic side-chains, ranging from 17.1 min for Trp to 4.8 min for Cys. In contrast, coefficients derived from substitutions at the N-terminus showed relatively small differences from the internal coefficients. Subsequent prediction of peptide retention time, within an error of just 0.4 min, was achieved by a predictive algorithm using a combination of internal coefficients and a weighted coefficient for the C-terminal residue.

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“…Using this RP-HPLCbased approach, most researchers have carried out regression analysis of a random collection of peptides to relate peptide hydrophobicity to peptide retention behavior. 3,[19][20][21][22][23][24]27,[29][30][31] The preferred approach of our laboratory is to apply RP-HPLC to the separation of mixtures of synthetic model peptides with just single amino acid substitutions in a defined peptide sequence. We believe that such an approach eliminates such concerns as the relative frequency with which a particular amino acid appears compared to others in a random collection of peptides.…”

Section: Introductionmentioning

confidence: 99%

Determination of intrinsic hydrophilicity/hydrophobicity of amino acid side chains in peptides in the absence of nearest‐neighbor or conformational effects

2005

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Understanding the hydrophilicity/hydrophobicity of amino acid side chains in peptides/proteins is one the most important aspects of biology. Though many hydrophilicity/hydrophobicity scales have been generated, an "intrinsic" scale has yet to be achieved. "Intrinsic" implies the maximum possible hydrophilicity/hydrophobicity of side chains in the absence of nearest-neighbor or conformational effects that would decrease the full expression of the side-chain hydrophilicity/hydrophobicity when the side chain is in a polypeptide chain. Such a scale is the fundamental starting point for determining the parameters that affect side-chain hydrophobicity and for quantifying such effects in peptides and proteins. A 10-residue peptide sequence, Ac-X-G-A-K-G-A-G-V-G-L-amide, was designed to enable the determination of the intrinsic values, where position X was substituted by all 20 naturally occurring amino acids and norvaline, norleucine, and ornithine. The coefficients were determined by reversed-phase high-performance liquid chromatography using six different mobile phase conditions involving different pH values (2, 5, and 7), ion-pairing reagents, and the presence and absence of different salts. The results show that the intrinsic hydrophilicity/hydrophobicity of amino acid side chains in peptides (proteins) is independent of pH, buffer conditions, or whether C(8) or C(18) reversed-phase columns were used for 17 side chains (Gly, Ala, Cys, Pro, Val, nVal, Leu, nLeu, Ile, Met, Tyr, Phe, Trp, Ser, Thr, Asn, and Gln) and dependent on pH and buffer conditions, including the type of salt or ion-pairing reagent for potentially charged side chains (Orn, Lys, His, Arg, Asp, and Glu).

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Determination of solute descriptors of tripeptide derivatives based on high-throughput gradient high-performance liquid chromatography retention data

Cited by 44 publications

References 32 publications

The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship

The correlation and prediction of the solubility of compounds in water using an amended solvation energy relationship

Requirements for prediction of peptide retention time in reversed-phase high-performance liquid chromatography: Hydrophilicity/hydrophobicity of side-chains at the N- and C-termini of peptides are dramatically affected by the end-groups and location

Determination of intrinsic hydrophilicity/hydrophobicity of amino acid side chains in peptides in the absence of nearest‐neighbor or conformational effects

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