A mapping of the interactions between a moth sex pheromone component and its receptor
(1996)- Abstract
- A number of analogues of (Z)-5-decenyl acetate (1), a pheromone component of the turnip moth, Agrotis segetum, have been synthesised and tested by using single-cell electrophysiology, in order to investigate the relationships between structure and activity, and to elucidate the interactions between 1 and its receptor. Molecular mechanics and ab initio quantum mechanical calculations have been used to provide information on molecular properties, conformational energies and electrostatic potentials, which have been used in the interpretation of the observed activities.
A study of alkyl ether and enol ether analogues of 1 and (Z)-5-dodecenyl acetate (2) provides support for a previous hypothesis that the terminal chain of... (More) - A number of analogues of (Z)-5-decenyl acetate (1), a pheromone component of the turnip moth, Agrotis segetum, have been synthesised and tested by using single-cell electrophysiology, in order to investigate the relationships between structure and activity, and to elucidate the interactions between 1 and its receptor. Molecular mechanics and ab initio quantum mechanical calculations have been used to provide information on molecular properties, conformational energies and electrostatic potentials, which have been used in the interpretation of the observed activities.
A study of alkyl ether and enol ether analogues of 1 and (Z)-5-dodecenyl acetate (2) provides support for a previous hypothesis that the terminal chain of chain-elongated analogues of 1 adopts a loop conformation in their bioactive conformations.
The acetate group of 1 has been replaced by various functional groups, which may serve as bioisosteres, to elucidate how and in what directions the acetate group interacts with the receptor site.
A quantitative model, for the relationship between the activity for a large number of analogues of 1 and the structural characteristics of the analogues, was developed by using three-dimensional quantitative structure-activity relationship (3D-QSAR) methodology, including partial least square (PLS) analyses.
The bioactive conformation of 1, a cisoid conformation, and the chiral recognition of the receptor was probed using constrained analogues, the enantiomers of cis- and trans-3-(4-propyl-cyclopent-2-enyl) propyl acetate. (Less) - Abstract (Swedish)
- Popular Abstract in Swedish
Insekter kommunicerar med dofter. De artspecifika kemiska substanser som används mellan individer kallas feromoner. Hos sädesbroddflyet, Agrotis segetum, producerar honan en "parfym", ett sexualferomon som består av flera komponenter, för att locka till sig en hane. På hanens antenner finns lukthår med särskilda motagare, receptorer, som används för att detektera honans parfym.
En av sädesbroddflyets sexualferomonkomponenter, (Z)-5-decenylacetat, och dess receptor har studerats i detta arbete. Eftersom den tre-dimensionella strukturen av receptorn inte är känd har strukturanaloger till den naturliga komponenten syntetiserats och deras biologiska aktivitet mätts. Med... (More) - Popular Abstract in Swedish
Insekter kommunicerar med dofter. De artspecifika kemiska substanser som används mellan individer kallas feromoner. Hos sädesbroddflyet, Agrotis segetum, producerar honan en "parfym", ett sexualferomon som består av flera komponenter, för att locka till sig en hane. På hanens antenner finns lukthår med särskilda motagare, receptorer, som används för att detektera honans parfym.
En av sädesbroddflyets sexualferomonkomponenter, (Z)-5-decenylacetat, och dess receptor har studerats i detta arbete. Eftersom den tre-dimensionella strukturen av receptorn inte är känd har strukturanaloger till den naturliga komponenten syntetiserats och deras biologiska aktivitet mätts. Med molekylmekanik och ab initio beräkningar har information om analogernas molekylära egenskaper, som geometrier, konformations- energier och elektrostatiska egenskaper, erhållits. Utifrån dessa resultat kan man förstå hur (Z)-5-decenylacetat och dess receptor interagerar.
Målet med dessa struktur-aktivitetsstudier har varit att bestämma den biologiskt aktiva konformationen av den naturliga feromonkomponenten samt receptorns kirala igenkänning. Den biologiskt aktiva konformationen hos kedjeförlängda analoger har studerats. Vidare har den polära gruppen, esterfunktionen, hos den naturliga feromonkomponenten och dess samverkan med receptorn undersökts. Slutligen har 3D-QSAR- metodologin använts för att utveckla en kvantitativ modell för sambandet mellan biologisk aktivitet och molekylära/strukturella egenskaper hos ett stort antal analoger till den naturliga feromonkomponenten. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/28828
- author
- Gustavsson, Anna-Lena
- supervisor
- opponent
-
- Dr Björkling, Fredrik, Leo Pharmaceutical Products, Denmark
- publishing date
- 1996
- type
- Thesis
- publication status
- published
- subject
- keywords
- Organic chemistry, chiral recognition, bioactive conformation, structure-activity, Agrotis segetum, (Z)-5-decenyl acetate, pheromone analogues, single-cell electrophysiology, molecular mechanics, ab initio, MM3, quantum mechanical calculations, 3D-QSAR, bioisosteres, Organisk kemi
- pages
- 71 pages
- publisher
- Organic Chemistry, Lund University
- defense location
- Center for Chemistry, lecture hall D
- defense date
- 1996-12-06 10:15:00
- external identifiers
-
- other:ISRN: LUNDL/NKOK-1035-SE
- ISBN
- 91-628-2253-5
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)
- id
- 5f631318-fc87-49a8-a6bb-423aa62179f1 (old id 28828)
- date added to LUP
- 2016-04-04 11:07:57
- date last changed
- 2018-11-21 21:02:52
@phdthesis{5f631318-fc87-49a8-a6bb-423aa62179f1,
abstract = {{A number of analogues of (Z)-5-decenyl acetate (1), a pheromone component of the turnip moth, Agrotis segetum, have been synthesised and tested by using single-cell electrophysiology, in order to investigate the relationships between structure and activity, and to elucidate the interactions between 1 and its receptor. Molecular mechanics and ab initio quantum mechanical calculations have been used to provide information on molecular properties, conformational energies and electrostatic potentials, which have been used in the interpretation of the observed activities.<br/><br>
<br/><br>
A study of alkyl ether and enol ether analogues of 1 and (Z)-5-dodecenyl acetate (2) provides support for a previous hypothesis that the terminal chain of chain-elongated analogues of 1 adopts a loop conformation in their bioactive conformations.<br/><br>
<br/><br>
The acetate group of 1 has been replaced by various functional groups, which may serve as bioisosteres, to elucidate how and in what directions the acetate group interacts with the receptor site.<br/><br>
<br/><br>
A quantitative model, for the relationship between the activity for a large number of analogues of 1 and the structural characteristics of the analogues, was developed by using three-dimensional quantitative structure-activity relationship (3D-QSAR) methodology, including partial least square (PLS) analyses.<br/><br>
<br/><br>
The bioactive conformation of 1, a cisoid conformation, and the chiral recognition of the receptor was probed using constrained analogues, the enantiomers of cis- and trans-3-(4-propyl-cyclopent-2-enyl) propyl acetate.}},
author = {{Gustavsson, Anna-Lena}},
isbn = {{91-628-2253-5}},
keywords = {{Organic chemistry; chiral recognition; bioactive conformation; structure-activity; Agrotis segetum; (Z)-5-decenyl acetate; pheromone analogues; single-cell electrophysiology; molecular mechanics; ab initio; MM3; quantum mechanical calculations; 3D-QSAR; bioisosteres; Organisk kemi}},
language = {{eng}},
publisher = {{Organic Chemistry, Lund University}},
title = {{A mapping of the interactions between a moth sex pheromone component and its receptor}},
year = {{1996}},
}