Identification of constrained peptidomimetic chemotypes as HIV protease inhibitors

Calugi, Chiara; Guarna, Antonio; Trabocchi, Andrea

doi:10.1016/j.ejmech.2014.07.049

Cited by 9 publications

(5 citation statements)

References 27 publications

(38 reference statements)

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“…Additionally these compounds satisfy all the requirements needed for the peptidomimetic chemistry, as they are easily synthesized and decorated with functional groups, and are well-suited for solid-phase synthesis. These scaffolds revealed to be active hit compounds towards different targets, as they have been used as aspartyl protease inhibitors [84,85] and NGF-agonists [86].…”

Section: Case Study 3: Our Contribution To the Chemical Genetics Smentioning

confidence: 99%

Diversity-Oriented Synthesis as a Tool for Chemical Genetics

2014

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Chemical genetics is an approach for identifying small molecules with the ability to induce a biological phenotype or to interact with a particular gene product, and it is an emerging tool for lead generation in drug discovery. Accordingly, there is a need for efficient and versatile synthetic processes capable of generating complex and diverse molecular libraries, and Diversity-Oriented Synthesis (DOS) of small molecules is the concept of choice to give access to new chemotypes with high chemical diversity. In this review, the combination of chemical genetics and diversity-oriented synthesis to identify new chemotypes as hit compounds in chemical biology and drug discovery is reported, giving an overview of basic concepts and selected case studies.

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Section: Case Study 3: Our Contribution To the Chemical Genetics Smentioning

confidence: 99%

Diversity-Oriented Synthesis as a Tool for Chemical Genetics

2014

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“…A library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was screened against HIV protease, resulting in the identification of hit compounds possessing IC 50 values in the sub-micromolar range, and showing the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues [13].…”

Section: Library Applicationsmentioning

confidence: 99%

Combinatorial Chemistry Online Volume 16, Issue 11, November 2014

Terrett

2014

Combinatorial Chemistry - an Online Journal

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“…Peptidomimetic inhibitors are capable of interacting with biological targets and producing the same therapeutic effects as native peptides. Using peptidomimetic inhibitors can eliminate some of the drawbacks of using native peptides, including proteolysis and low bioavailability (Vankadara et al 2021 ; Paul et al 2021 ; Somboon et al 2021 ; Wang et al 2022 ; Phoo et al 2018 ; Colarusso et al 2022 ; Ezat et al 2015 ; Mostafa et al 2014 ; Ibrahim et al 2013 ; Saleh and Elshemey 2017 ; Calugi et al 2014 ; Frecer et al 2008 ).…”

Section: Introductionmentioning

confidence: 99%

In-silico study: docking simulation and molecular dynamics of peptidomimetic fullerene-based derivatives against SARS-CoV-2 Mpro

Saleh

2023

3 Biotech

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COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, has become a global pandemic resulting in significant morbidity and mortality. This study presents 12 new peptidomimetic fullerene-based derivatives in three groups that are investigated theoretically as SARS-CoV-2 M pro inhibitors to increase the chance of treating COVID-19. Studied compounds are designed and optimized at B88-LYP/DZVP method. Molecular descriptors results show the stability and reactivity of the compounds with M pro , especially in the 3rd group (Ser compounds). However, Lipinski's Rule of Five values indicates that the compounds are not suitable as oral drugs. Furthermore, molecular docking simulations are carried out to investigate the binding affinity and interaction modes of the top five compounds (compounds 1, 9, 11, 2, and 10) with the M pro protein, which have the lowest binding energy. Molecular dynamics simulations are also performed to evaluate the stability of the protein–ligand complexes with compounds 1 and 9 and compare them with natural substrate interaction. The analysis of RMSD, H-bonds, Rg, and SASA indicates that both compounds 1 (Gly-α acid) and 9 (Ser-α acid) have good stability and strong binding affinity with the M pro protein. However, compound 9 shows slightly better stability and binding affinity compared to compound 1.

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Identification of constrained peptidomimetic chemotypes as HIV protease inhibitors

Cited by 9 publications

References 27 publications

Diversity-Oriented Synthesis as a Tool for Chemical Genetics

Diversity-Oriented Synthesis as a Tool for Chemical Genetics

Combinatorial Chemistry Online Volume 16, Issue 11, November 2014

In-silico study: docking simulation and molecular dynamics of peptidomimetic fullerene-based derivatives against SARS-CoV-2 Mpro

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