| Title: | Scaffold hopping and bioisosteric replacements based on binding site alignments |
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| Authors: | ID Lešnik, Samo (Author)
ID Konc, Janez (Author)
ID Janežič, Dušanka (Author) |
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| Files: |  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
 http://hrcak.srce.hr/171908
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| Language: | English |
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| Work type: | Scientific work |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: | FKKT - Faculty of Chemistry and Chemical Engineering
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| 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. |
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| Keywords: | bioisosteres, scaffold hopping, protein alignment, ProBiS, drug design, analysis methods, matter structure, modelling |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2016 |
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| Number of pages: | str. 2-7 |
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| Numbering: | Letn. 89, št. 4 |
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| PID: | 20.500.12556/DKUM-66666  |
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| ISSN: | 0011-1643 |
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| UDC: | 543.2/.9 |
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| ISSN on article: | 0011-1643 |
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| COBISS.SI-ID: | 6066458 |
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| DOI: | 10.5562/cca2993 |
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| NUK URN: | URN:SI:UM:DK:9O3KKKIB |
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| Publication date in DKUM: | 05.07.2017 |
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| Views: | 1381 |
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| Downloads: | 466 |
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| Metadata: |    |
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| Categories: | Misc.
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