Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery
State-of-the-art delivery systems currently rely on chemical synthesis routes for drug encapsulation. However, these methods have inherent drawbacks concerning toxicity, selectivity, and the potential for burst release. To overcome these limitations, the enzymatic synthesis of polymer-drug conjugate...
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cracsoc:10.26434/chemrxiv-2024-pzclt-v2 2024-09-30T14:25:02+00:00 Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery R. Figueiredo, Pedro J.D. Silvestre, Armando F. Sousa, Andreia T.P. Carvalho, Alexandra 2024 http://dx.doi.org/10.26434/chemrxiv-2024-pzclt-v2 https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66cdda9d20ac769e5f02f47b/original/reactivity-of-pseudozyma-antarctica-lipase-b-towards-the-synthesis-of-end-capped-polycaprolactone-for-drug-delivery.pdf unknown American Chemical Society (ACS) https://creativecommons.org/licenses/by-nc-nd/4.0/ posted-content 2024 cracsoc https://doi.org/10.26434/chemrxiv-2024-pzclt-v2 2024-09-05T04:08:01Z State-of-the-art delivery systems currently rely on chemical synthesis routes for drug encapsulation. However, these methods have inherent drawbacks concerning toxicity, selectivity, and the potential for burst release. To overcome these limitations, the enzymatic synthesis of polymer-drug conjugates emerges as a promising alternative to promote ecofriendliness and safety in production and grants precise control over the resulting structures. In this study, we delved into the reactivity of Pseudozyma (Candida) antarctica lipase B for polyesters’ capping with small molecules. For that purpose, Quantum Mechanics/Molecular Mechanics simulations were used to predict the conjugation reactions. These predictions were translated to the laboratory, where the enzymatic reactions were replicated, subsequently benchmarking them against metal-catalysed reactions. The outcome of our experiments was the successful generation of end-capped oligo/polycaprolactone, with their molecular weights spanning from 540 to 2600 g/mol with an enzymatic approach, and slightly higher when applying conventional catalysis, and with isolation yields up to 68.4%. This work underscores the potential of enzyme-driven strategies in fabricating precisely engineered drug delivery Other/Unknown Material Antarc* Antarctica ACS Publications |
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ACS Publications |
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State-of-the-art delivery systems currently rely on chemical synthesis routes for drug encapsulation. However, these methods have inherent drawbacks concerning toxicity, selectivity, and the potential for burst release. To overcome these limitations, the enzymatic synthesis of polymer-drug conjugates emerges as a promising alternative to promote ecofriendliness and safety in production and grants precise control over the resulting structures. In this study, we delved into the reactivity of Pseudozyma (Candida) antarctica lipase B for polyesters’ capping with small molecules. For that purpose, Quantum Mechanics/Molecular Mechanics simulations were used to predict the conjugation reactions. These predictions were translated to the laboratory, where the enzymatic reactions were replicated, subsequently benchmarking them against metal-catalysed reactions. The outcome of our experiments was the successful generation of end-capped oligo/polycaprolactone, with their molecular weights spanning from 540 to 2600 g/mol with an enzymatic approach, and slightly higher when applying conventional catalysis, and with isolation yields up to 68.4%. This work underscores the potential of enzyme-driven strategies in fabricating precisely engineered drug delivery |
format |
Other/Unknown Material |
author |
R. Figueiredo, Pedro J.D. Silvestre, Armando F. Sousa, Andreia T.P. Carvalho, Alexandra |
spellingShingle |
R. Figueiredo, Pedro J.D. Silvestre, Armando F. Sousa, Andreia T.P. Carvalho, Alexandra Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery |
author_facet |
R. Figueiredo, Pedro J.D. Silvestre, Armando F. Sousa, Andreia T.P. Carvalho, Alexandra |
author_sort |
R. Figueiredo, Pedro |
title |
Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery |
title_short |
Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery |
title_full |
Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery |
title_fullStr |
Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery |
title_full_unstemmed |
Reactivity of Pseudozyma antarctica lipase B towards the Synthesis of End-capped Polycaprolactone for Drug Delivery |
title_sort |
reactivity of pseudozyma antarctica lipase b towards the synthesis of end-capped polycaprolactone for drug delivery |
publisher |
American Chemical Society (ACS) |
publishDate |
2024 |
url |
http://dx.doi.org/10.26434/chemrxiv-2024-pzclt-v2 https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66cdda9d20ac769e5f02f47b/original/reactivity-of-pseudozyma-antarctica-lipase-b-towards-the-synthesis-of-end-capped-polycaprolactone-for-drug-delivery.pdf |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_rights |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
op_doi |
https://doi.org/10.26434/chemrxiv-2024-pzclt-v2 |
_version_ |
1811643184801906688 |