Subject: Summary of responses for QSAR question.

From: "ADRIAN STEVENS, DEPT. OF CHEMISTRY, UNI. OF PORTSMOUTH" <[email-masked]>
Date: Wed, 14 Dec 94 10:54 GMT

Dear Netters,

When I put a question to the next, I promised that I would post a summary
of the responses that I recieved.  Therefore, as promised, I have included
the list below

I tried to make a point of replying to everyone who responded, thanking them
for the references.  However, in case I missed off anyone, then I would just
like to say thank you now.

Adrian Stevens,
University of Portsmouth.

PS I hope that everyone has a very happy Xmas/Festivity/Holiday/Whatever!

------------------------------------------------------------------------

Q.S.A.R. Responses...

------------------------------------------------------------------------

From:	CBS%UK.AC.NSFNET-RELAY::IT.IRBM::KOEHLER  2-DEC-1994 12:54:16.12
To:	stevensa
CC:	
Subj:	QSAR Response

Dear Adrian:

   For QSAR's of enzymes, the following would seem a particularly appropriate
and recent reference:

Nomizu, M.; Iwaki, T.; Yamashita, T.; Inagaki, Y.; Asano, K.; Akamatsu, M.;
Fujita, T. Quantitative structure-activity relationship (QSAR) study of
elastase substrates and inhibitors.  Int. J. Pept. Protein. Res.   1993, 42,
216-226. 

Abstract:  One hundred Suc-X-Y-Ala-pNA peptides: (Suc: succinyl, pNA:
p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, alpha-aminobutyric
acid, norvaline, norleucine) were synthesized and their reaction constants with
porcine pancreatic elastase (Km, kcat and kcat/Km) were determined. These
reaction constants were quantitatively analyzed using the Free-Wilson/Fujita-
Ban method. The contribution of amino acid side chains to the reaction
constants Km, kcat and kcat/Km, expressed logarithmically, was found to be
additive. On the other hand, 19 elastase inhibitors of the general formula
CF3CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition
constants were compared with the Michaelis constant for the corresponding
substrates and analyzed using free-energy-related substituent constants. In the
analysis of amino acid side chains in the Y position, the Ki value of the
inhibitor was generally correlated to the Km value of the substrate, which
corresponded to the inhibitor, thus confirming the validity of the equation.
log(1/Ki) = 1.271 log(1/Km) + 4.831 This study may serve as a prototypical
approach to unraveling structure-activity relationships of peptide substrates
and inhibitors of medicinal or agricultural importance. 

   If you are interested in 3D-QSAR and enzymes, check the following
references out:

(1) DePriest, S. A.; Mayer, D.; Naylor, C. B.; Marshall, G. R. 3D-QSAR of    
    angiotensin-converting enzyme and thermolysin inhibitors:  a comparison of
    CoMFA models based on deduced and experimentally determined active site
    geometries. J. Am. Chem. Soc.   1993, 115, 5372-84. 
(2) Motoc, I.; Sit, S. Y.; Harte, W. E.; Balasubramanian, N.; Wright, J. J.
    3-Hydroxy-3-methylglutaryl-Coenzyme A Reductase: Molecular Modeling,
    Three-Dimensional structure-activity relationships, inhibitor design.  QSAR
    1991, 10, 30.
(3) Sit, S. Y.; Parker, R. A.; Motoc, I.; Han, W.; Balasubramanian, N.; Catt, J.
    D.; Brown, P. J.; Harte, W. E.; Thompson, M. D.; Wright, J. J. Synthesis,  
    biological profile, and quantitative structure-activity relationship of a
    series of novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
    J. Med. Chem.   1990, 33, 2982-99. 
(4) Waller, C. L.; McKinney, J. D. Comparative molecular field analysis of
    polyhalogenated dibenzo-p-dioxins, dibenzofurans, and biphenyls.  J. Med.
    Chem. 1992, 35, 3660-6. 
(5) Waller, C. L.; Marshall, G. R. Three-dimensional quantitative
    structure-activity relationship of angiotensin-converting enzyme and
    thermolysin inhibitors.  II.  A Comparison of CoMFA models incorporating
    molecular orbital fields and desolvation free energies based on
    active-analog and complementry-receptor-field alignment rules.  J. Med.
    Chem. 1993, 36, 2390-2403. 
(6) Waller, C. L.; Oprea, T. I.; Giolitti, A.; Marshall, G. R. Three-dimensional
    QSAR of human immunodeficiency virus (I) protease inhibitors.  1.  A CoMFA
    study employing experimentally-determined alignment rules.  J. Med. Chem.  
    1993, 36, 4152-4160. 

    Ciao,

 ------------------------------------------------------------------
| Konrad Koehler              |  Computational Chemistry Group     |
| internet:  [email-masked]  |  Department of Medicinal Chemistry |
|                             |  IRBM                              |
| telephone: +39-6-910-93606  |  Via Pontina Km. 30,600            |
| fax:       +39-6-910-93225  |  00040 Pomezia (Roma)              |
|                             |  Italy                             |
 ------------------------------------------------------------------

--------------------------------------------------------------------------

From:	CBS%UK.AC.NSFNET-RELAY::GOV.EPA.HERL.THOR::WALLER  2-DEC-1994 13:20:23.68
To:	STEVENSA
CC:	
Subj:	Re: CCL:Introductory Q.S.A.R. References.?

As a graduate student I found Yvonne Martin's Quantitative Drug 
Design (Marcel Dekker, New York) an extremely useful introductory
text.

********************************************************************
*Chris L. Waller, Ph.D.                          PHONE 919-541-7976*
*Research Chemist                                FAX   919-541-5394*
[email-masked]                                          *
*Pharmacokinetics Branch (MD-74)                                   *
*ETD/HERL/USEPA                                                    *
*Research Triangle Park, NC 27711                                  *
*                                                                  *
*Disclaimer: Mention of trade names or products does not constitute*
*endorsement by the United States Environmental Protection Agency. *
********************************************************************

---------------------------------------------------------------------------

From:	CBS%UK.AC.NSFNET-RELAY::EDU.CWRU.CHEM.CWGK::FERCU  2-DEC-1994 13:30:06.08
To:	STEVENSA
CC:	
Subj:	QSAR Response

Dear Adrian,

The most recent book I know of is "QSAR: Hansch analysis and related
approaches" by Hugo Kubinyi (VCH: Weinheim, 1993, 240p). It has a good review
on the most used QSAR parameters. Besides the well known Hansch analysis, other 
models are described, such as Free Wilson, pattern recognition techniques, 
3D QSAR models (CoMFA). Almost half of the book is dedicated to applications.
Over 1000 references.
A reduced version of this book can be found in the new edition of "Burger's
Medicinal Chemistry and Drug Discovery" (Wolff, M. E., Ed., Wiley: New York, 
Vol.1, 5th ed., 1994).

Regards,
Dan Fercu

Dan Fercu
Computational Chemist
Department of Chemistry
Case Western Reserve University
[email-masked]

---------------------------------------------------------------------------

From:	CBS%UK.AC.NSFNET-RELAY::COM.ABBOTT.RANDB::CMDA::MARTIN  2-DEC-1994 14:37:14.81
To:	STEVENSA
CC:	
Subj:	Re: CCL:Introductory Q.S.A.R. References.?

The classic book, now out of print but maybe available in your library,
is mine: "Quantitative Drug Design", published by Marcel Dekker.

There is also a nice introduction in Comprehensive Medicinal Chemistry,
Vol 4, edited by Hansch, Sammes, & Taylor. Pergamon.

Methods in Enzymology vol 203 edited by Langone also has several 
interesting chapters.

Finally, there is the interesting book edited by Kubinyi "3D QSAR
in Drug Design". ESCOM, 1994.

Yvonne Martin
Abbott Laboratories

----------------------------------------------------------------------------

From:	CBS%UK.AC.NSFNET-RELAY::UK.CO.OXMOL::SCOFFIN  5-DEC-1994 08:32:30.54
To:	STEVENSA
CC:	
Subj:	QSAR Response...

Adrian,

There are a number of good introductory level texts, depending on
what you are looking for; i.e. Hansch Analysis or 3D-QSAR.  For the latter
I would try '3D QSAR in Drug Design'; H.Kubinyi, ESCOM, 1994.

There are good books by Yvonne Martin, Reiner Franke, Han van de Waterbeemd
and Mike Tute on various aspects of 2D and 3D QSAR, I can find more
specific references if that will help...

Good luck in your search,

Rob Scoffin
===========

Robert Scoffin         ________________
QSAR Product Manager  |  ##   ##   ##  |
Oxford Molecular Ltd  |   ##  ##  ##   |
The Magdalen Centre   |    ## ## ##    |
Oxford Science Park   |     ######     |
Oxford OX4 4GA        |       ##       |
Tel: (0865)784600     |       ##       |
Fax: (0865)784601     |      ####      |
Mobile: (0378) 210813  ----------------

--------------------------------------------------------------------------

From:	CBS%UK.AC.NSFNET-RELAY::ORG.ACS::BEP96  5-DEC-1994 14:25:59.89
To:	stevensa
CC:	
Subj:	QSAR Response

Your message was forwarded to me by Nan Butterworth.  The following book will
be available later this month.  Please note that volume I is designed to
introduce the reader to QSAR.  If you have any specific questions please do
not hestitate to email me at [email-masked].  

Barbara Pralle
Acquisitions Editor

TWO VOLUME SET

"BOOK TITLE (Vol. 1):"	Exploring QSAR
"SUBTITLE:"		Fundamentals and Applications in Chemistry and Biology

AUTHORS(S):		Corwin Hansch and Albert Leo

"BOOK TITLE (Vol. 2):"	Exploring QSAR
"SUBTITLE:"		Hydrophobic, Electronic, and Steric Constants

AUTHORS(S):		Corwin Hansch, Albert Leo, David Hoekman

ISBN: 0-8412-2993-7
PRICE: $99.95
PUBLICATION DATE: December 1994

SIZE: 7 X 10 inches (Vol. 1) 8 1/2 X 11 inces (Vol. 2)
BINDING: Clothbound (Vol. 1) Clothbound (Vol. 2) 
ESTIMATED PAGES: 900 

AUDIENCE/LEVEL:
Medicinal chemists, agrochemical chemists, toxicologists, environmental
scientists, computational chemists, pharmaceutical scientists, scientists
involved in computer-assisted drug discovery, bioorganic chemists, pesticide
chemists and formulators, analytical chemists working with partition
coefficient measurements.  

HIGHLIGHTS:

Investigates the interaction of organic compounds with various forms of life
including macromolecules, enzymes, organelles, etc.

Introduces the Hammett equation and its applications.

Discusses the design of bioactive compounds.

Includes extensive tables of approximately 17,000 partition coefficients from
octanol/water as well as a comprehensive listing of electronic and steric
parameters used in the design and study of bioactive organic compounds.  

-----------------------------------------------------------------------------
				End of list
-----------------------------------------------------------------------------