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Title:Scaffold hopping and bioisosteric replacements based on binding site alignments
Authors:ID Lešnik, Samo (Author)
ID Konc, Janez (Author)
ID Janežič, Dušanka (Author)
Files:.pdf Croatica_Chemica_Acta_2016_Lesnik,_Konc,_Janezic_Scaffold_Hopping_and_Bioisosteric_Replacements_Based_on_Binding_Site_Alignments.pdf (2,30 MB)
MD5: 4A8817398F7DC47689CF1CFBE5E92B4E
PID: 20.500.12556/dkum/417e9b18-64f2-4159-a27a-441f311be5df
 
URL http://hrcak.srce.hr/171908
 
Language:English
Work type:Scientific work
Typology:1.01 - Original Scientific Article
Organization:FKKT - Faculty of Chemistry and Chemical Engineering
Abstract:Bioisosteric replacements and scaffold hopping play an important role in modern drug discovery and design, as they enable the change of either a core scaffold or substitutes in a drug structure, thereby facilitating optimization of pharmacokinetic properties and patenting, while the drug retains its activity. A new knowledge-based method was developed to obtain bioisosteric or scaffold replacements based on the extensive data existing in the Protein Data Bank. The method uses all-against-all ProBiS-based protein superimposition to identify ligand fragments that overlap in similar binding sites and could therefore be considered as bioisosteric replacements. The method was demonstrated on a specific example of drug candidate – a nanomolar butyrylcholinesterase inhibitor, on which bioisosteric replacements of the three ring fragments were performed. The new molecule containing bioisosteric replacements was evaluated virtually using AutoDock Vina; a similar score for the original and the compound with replacements was obtained, suggesting that the newly designed bioisostere compound might retain the potency of the original inhibitor.
Keywords:bioisosteres, scaffold hopping, protein alignment, ProBiS, drug design, analysis methods, matter structure, modelling
Publication status:Published
Publication version:Version of Record
Year of publishing:2016
Number of pages:str. 2-7
Numbering:Letn. 89, št. 4
PID:20.500.12556/DKUM-66666 New window
ISSN:0011-1643
UDC:543.2/.9
ISSN on article:0011-1643
COBISS.SI-ID:6066458 New window
DOI:10.5562/cca2993 New window
NUK URN:URN:SI:UM:DK:9O3KKKIB
Publication date in DKUM:05.07.2017
Views:1237
Downloads:431
Metadata:XML DC-XML DC-RDF
Categories:Misc.
:
LEŠNIK, Samo, KONC, Janez and JANEŽIČ, Dušanka, 2016, Scaffold hopping and bioisosteric replacements based on binding site alignments. Croatica Chemica Acta [online]. 2016. Vol. 89, no. 4, p. 2–7. [Accessed 23 January 2025]. DOI 10.5562/cca2993. Retrieved from: https://dk.um.si/IzpisGradiva.php?lang=eng&id=66666
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Record is a part of a journal

Title:Croatica Chemica Acta
Shortened title:Croat. Chem. Acta
Publisher:Hrvatsko kemijsko društvo
ISSN:0011-1643
COBISS.SI-ID:22807 New window

Document is financed by a project

Funder:ARRS - Slovenian Research Agency
Project number:P1-0002
Name:Matematične in simulacijske metode pri obravnavi strukture in dinamike molekul ter neravnovesne statistične mehanike

Licences

License:CC BY 4.0, Creative Commons Attribution 4.0 International
Link:http://creativecommons.org/licenses/by/4.0/
Description:This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:05.07.2017

Secondary language

Language:Slovenian
Keywords:bioizosteri, zamenjava skeleta, poravnava proteinov, ProBis, racionalno načrtovanje učinkovin, analizne metode, struktura snovi, modeliranje


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