Subject: logP and solubility for Amino Acids and peptides

From: Tomoko Niwa <[email-masked]>
Date: Thu, 20 Nov 1997 11:05:46 +0900

Dear CCL:

Wang Arthur wrote:

> We are currently on a project of de novo protein design. A set of scales 
> which describe the hydrophobicities of the natural amino acids is what we 
> badly need. 

> (2) LogP values for the 20 natural amino acids and oligopeptides (up to 
> buta- or pentapeptides). 

Please check the following papers: 

Tomoko Sotomatsu-Niwa, Akio Ogino, Evaluation of the hydrophobic
parameters of the amino acid side chains of peptides and their 
application in QSAR and conformational studies, THEOCHEM (1997), 
392, 43-54.
 
We statistically analyzed the experimentally determined 1-octanol/water
partition coefficient, log P, of a wide variety of N-acetyl-di- and tripeptide
amides and unblocked di- and tripeptides to evaluated the hydrophobic
parameters of the amino acid side chains of peptides.  For blocked peptides,
hydrophobic parameters were defined for amino acids having un-ionizable and
ionizable side chains.  For unblocked peptides, hydrophobic parameters were
evaluated for 12 amino acids with un-ionizable side chains.  In order to
estimate the hydrophobic parameters for unnatural and ionizable amino acids, a
procedure was developed based on the relationship between our hydrophobic
parameters and the log P values of model amino acids calculated by the fragment
constant method.  Use of the hydrophobic parameters in quantitative
structure-activity relationship (QSAR) studies of bioactive peptides and
conformational studies of proteins have also been presented.
(Our method is valid for the log P values for buta- or pentapeptides. ) 

Abraham, Donald J.; Leo, Albert J., Extension of the fragment method to
calculate amino acid zwitterion and side chain partition coefficients,
Proteins:  Struct., Funct., Genet. (1987), 2(2), 130-52

Leo, A. J., Computer calculation of peptide hydrophobicity, Pharmacochem. Libr.
(1991), 16(QSAR:  Ration. Approaches Des. Bioact. Compd.), 349-52

Fauchere, Jean Luc; Charton, Marvin; Kier, Lemont B.; Verloop, Arie; Pliska,
Vladimir, Amino acid side chain parameters for correlation studies in biology
and pharmacology, Int. J. Pept. Protein Res.  DATE: 1988  VOLUME: 32  NUMBER: 4
PAGES: 269-78  

Akamatsu, Miki; Fujita, Toshio, Quantitative analyses of hydrophobicity of di-
to pentapeptides having unionizable side chains with substituent and structural
parameters, J. Pharm. Sci. (1992), 81(2), 164-74
   
Akamatsu, Miki; Okutani, Shinichi; Nakao, Kazuya; Hong, Nam Joo; Fujita,
Toshio, Hydrophobicity of N-acetyl-di- and tripeptide amides having unionizable
side chains and correlation with substituent and structural parameters, Quant.
Struct.-Act. Relat.  DATE: 1990  VOLUME: 9  NUMBER: 

Akamatsu, Miki; Yoshida, Yohji; Nakamura, Hideaki; Asao, Masaaki; Iwamura,
Hajime; Fujita, Toshio, Hydrophobicity of di- and tripeptides having
unionizable side chains and correlation with substituent and structural
parameters, Quant. Struct.-Act. Relat.  DATE: 1989  VOLUME: 8  NUMBER: 3

[8] R.-S. Tsai, B. Testa, N. El Tayar, P.-A. Carrupt, 
J. Chem. Soc. Parkin Trans. 2, (1991), 1797.
[9] P. Vallat, P. Gaillard, P.-A. Carrupt, R.-S. Tsai, 
B. Testa, Helv. Chim. Acta, 78 (1995), 471.
[11] W. E. Steinmetz, Quant. Struct.-Act. Relat., 14 (1995), 19.
[12] N. El Tayar, H. Karajiannis, H. van de Waterbeemd, 
Amino Acids, 8 (1995), 125.

Best Regards

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Tomoko Sotomatsu Niwa, Ph.D. 
Research Lab. Nippon Shinyaku Co., Ltd.
Nishiohji Hachijo Minami-ku Kyoto, 601 Japan
tel 075-321-9047, fax 075-321-9038
[email-masked]
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