Photopharmacology uses light to regulate the biological activity of drugs. This precise control is obtained through the incorporation of molecular photoswitches into bioactive molecules. A major challenge for photopharmacology is the rational design of photoswitchable drugs that show light-induced activation. Computer-aided drug design is an attractive approach toward more effective, targeted design. This thesis describes the application and evaluation of rational drug design methods for predicting and interpreting the light-dependent activity of photopharmacogical agents. A wide range of informed, computer-aided design strategies was applied to the development of light-controlled tools, spanning from antibiotics to chemotherapeutics. The employed computational methods included docking and MD simulations for structure-based design, database searches to investigate molecular geometries, DFT calculations to study electronic properties. Future efforts in rational photopharmacology will need a combination of different methodologies and approaches to shed more light on the optical control of bioactive compounds

Kobauri, Piermichele

English

University of Groningen

   University of GroningenRational drug design in photopharmacologyKobauri, PiermicheleDOI:10.33612/diss.213323038IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Kobauri, P. (2022). Rational drug design in photopharmacology. University of Groningen.https://doi.org/10.33612/diss.213323038CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 20-11-2022Stellingen  Behorende bij het proefschrift Rational drug design in photopharmacology door Piermichele Kobauri  1. After showing numerous proof-of-concept studies, photopharmacology should now aim at applications in real-world scenarios by attracting pharmaceutical industry’s attention.  2. Explicitly declared “hopes” are hardly valid scientific hypotheses. The photopharmacology community could use more appropriate terms, such as “working hypotheses” or “educated guesses”. Alternatively, we can introduce the neologism “hopethesis”. Angew. Chem., Int. Ed., 2013, 52, 9845−9848 and ACS Med. Chem. Lett., 2019, 10, 1341−1345  3. Electronic differences between (E)- and (Z)-azobenzene offer underexplored opportunities for molecular design in photopharmacology. Chapter 3 and 4  4. Docking scores cannot be treated as a meaningful approximation of binding free energies. J. Am. Chem. Soc., 2021, 143, 736−743  5. Chemistry, and science in general, would greatly benefit from closer collaborations between experimentalists and theorists, instead of sterile superiority claims and constant skirmishes.  6. Research groups pay a publication fee to publish articles, whose access requires a costly subscription paid by universities. In the reviewing process, referees work on a voluntary basis, while all the profit goes to publishing companies. Inexplicably, there are only limited collective movements in academia that fights such unfair practice.  7. It is more valuable to have an idea about why something is not working as expected than to have no idea about why something works.  8. Computational drug design not only saves time and money in the early stages of drug discovery, but it can also make the pharmaceutical industry more sustainable, thereby helping in the fight against global warming.  9. Workaholism should not be praised as it currently – and toxically – is in academic settings. Negligence of work-life balance in academia is a serious threat to the mental health of too many researchers in academia. Nat. Biotechnol., 2018, 36, 282–284  10. To counteract the ongoing reproducibility crisis in science, it is necessary to dedicate more laboratories around the world to the replication and validation of scientific results, following the example of the Center for Open Science. In an ideal evolution of the current publishing process, peer review could be expanded with concomitant peer replication. eLife, 2021, 10:e67995  11. On closer inspection, photopharmacology is a form of molecular enlightenment.  12. Scientific writing tends to be uncreative and repetitive. Short sentences are clear yet boring.  13. Every chemical reaction is a nanoscopic choreography, in which molecules are the dancers, temperature is the rhythm, and the solvent is the dance floor. 

Rational drug design in photopharmacology

   University of GroningenRational drug design in photopharmacologyKobauri, PiermicheleDOI:10.33612/diss.213323038IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Kobauri, P. (2022). Rational drug design in photopharmacology. [Thesis fully internal (DIV), University ofGroningen]. University of Groningen. https://doi.org/10.33612/diss.213323038CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 30-04-2023Stellingen  Behorende bij het proefschrift Rational drug design in photopharmacology door Piermichele Kobauri  1. After showing numerous proof-of-concept studies, photopharmacology should now aim at applications in real-world scenarios by attracting pharmaceutical industry’s attention.  2. Explicitly declared “hopes” are hardly valid scientific hypotheses. The photopharmacology community could use more appropriate terms, such as “working hypotheses” or “educated guesses”. Alternatively, we can introduce the neologism “hopethesis”. Angew. Chem., Int. Ed., 2013, 52, 9845−9848 and ACS Med. Chem. Lett., 2019, 10, 1341−1345  3. Electronic differences between (E)- and (Z)-azobenzene offer underexplored opportunities for molecular design in photopharmacology. Chapter 3 and 4  4. Docking scores cannot be treated as a meaningful approximation of binding free energies. J. Am. Chem. Soc., 2021, 143, 736−743  5. Chemistry, and science in general, would greatly benefit from closer collaborations between experimentalists and theorists, instead of sterile superiority claims and constant skirmishes.  6. Research groups pay a publication fee to publish articles, whose access requires a costly subscription paid by universities. In the reviewing process, referees work on a voluntary basis, while all the profit goes to publishing companies. Inexplicably, there are only limited collective movements in academia that fights such unfair practice.  7. It is more valuable to have an idea about why something is not working as expected than to have no idea about why something works.  8. Computational drug design not only saves time and money in the early stages of drug discovery, but it can also make the pharmaceutical industry more sustainable, thereby helping in the fight against global warming.  9. Workaholism should not be praised as it currently – and toxically – is in academic settings. Negligence of work-life balance in academia is a serious threat to the mental health of too many researchers in academia. Nat. Biotechnol., 2018, 36, 282–284  10. To counteract the ongoing reproducibility crisis in science, it is necessary to dedicate more laboratories around the world to the replication and validation of scientific results, following the example of the Center for Open Science. In an ideal evolution of the current publishing process, peer review could be expanded with concomitant peer replication. eLife, 2021, 10:e67995  11. On closer inspection, photopharmacology is a form of molecular enlightenment.  12. Scientific writing tends to be uncreative and repetitive. Short sentences are clear yet boring.  13. Every chemical reaction is a nanoscopic choreography, in which molecules are the dancers, temperature is the rhythm, and the solvent is the dance floor. 

ARTS repository - University of Groningen

   University of GroningenRational drug design in photopharmacologyKobauri, PiermicheleDOI:10.33612/diss.213323038IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Kobauri, P. (2022). Rational drug design in photopharmacology. University of Groningen.https://doi.org/10.33612/diss.213323038CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 08-06-2022Stellingen  Behorende bij het proefschrift Rational drug design in photopharmacology door Piermichele Kobauri  1. After showing numerous proof-of-concept studies, photopharmacology should now aim at applications in real-world scenarios by attracting pharmaceutical industry’s attention.  2. Explicitly declared “hopes” are hardly valid scientific hypotheses. The photopharmacology community could use more appropriate terms, such as “working hypotheses” or “educated guesses”. Alternatively, we can introduce the neologism “hopethesis”. Angew. Chem., Int. Ed., 2013, 52, 9845−9848 and ACS Med. Chem. Lett., 2019, 10, 1341−1345  3. Electronic differences between (E)- and (Z)-azobenzene offer underexplored opportunities for molecular design in photopharmacology. Chapter 3 and 4  4. Docking scores cannot be treated as a meaningful approximation of binding free energies. J. Am. Chem. Soc., 2021, 143, 736−743  5. Chemistry, and science in general, would greatly benefit from closer collaborations between experimentalists and theorists, instead of sterile superiority claims and constant skirmishes.  6. Research groups pay a publication fee to publish articles, whose access requires a costly subscription paid by universities. In the reviewing process, referees work on a voluntary basis, while all the profit goes to publishing companies. Inexplicably, there are only limited collective movements in academia that fights such unfair practice.  7. It is more valuable to have an idea about why something is not working as expected than to have no idea about why something works.  8. Computational drug design not only saves time and money in the early stages of drug discovery, but it can also make the pharmaceutical industry more sustainable, thereby helping in the fight against global warming.  9. Workaholism should not be praised as it currently – and toxically – is in academic settings. Negligence of work-life balance in academia is a serious threat to the mental health of too many researchers in academia. Nat. Biotechnol., 2018, 36, 282–284  10. To counteract the ongoing reproducibility crisis in science, it is necessary to dedicate more laboratories around the world to the replication and validation of scientific results, following the example of the Center for Open Science. In an ideal evolution of the current publishing process, peer review could be expanded with concomitant peer replication. eLife, 2021, 10:e67995  11. On closer inspection, photopharmacology is a form of molecular enlightenment.  12. Scientific writing tends to be uncreative and repetitive. Short sentences are clear yet boring.  13. Every chemical reaction is a nanoscopic choreography, in which molecules are the dancers, temperature is the rhythm, and the solvent is the dance floor. 

https://pure.rug.nl/ws/files/213323058/Propositions.pdf

Rational drug design in photopharmacology

Abstract

Similar works

Full text

Available Versions

University of Groningen

University of Groningen

ARTS repository - University of Groningen

ARTS repository - University of Groningen