The interaction of supramolecular anticancer drug amphiphiles with phospholipid membranes

Tang, Phu K; Manandhar, Anjela; Hu, William; Kang, Myungshim; Loverde, Sharon M.

doi:10.1039/d0na00697a

Cited by 3 publications

(3 citation statements)

References 75 publications

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“…Tamoxifen [204], Cytarabine [205], 5-Fluorouracil [206,207], Daunorubicin [208,209], β-Lapachone [210], Minerval [211], Miltefosine [212], Tofacitinib [213], Edelfosine [214], Miltefosine [214], Perifosine [214], Camptothecin [215,216], Pirarubicin, Ellipticine [217], Perillyl alcohol [218], Cisplatin [219,220], Doxorubicin [179,217,221], 5-fluorouracil [206];…”

Section: Application and Target Drugs And Pharmaceuticsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Section: Application and Target Drugs And Pharmaceuticsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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“…The initial stages of self-assembly are at microseconds to seconds time scales. For example, Tang and Manandhar et al used MD simulations to characterize the interactions of a similar DA system with a model membrane . More studies on these DAs using molecular dynamics (MD) simulations can be found elsewhere. ,,,, …”

Section: Introductionmentioning

confidence: 99%

“…For example, Tang and Manandhar et al used MD simulations to characterize the interactions of a similar DA system with a model membrane. 29 More studies on these DAs using molecular dynamics (MD) simulations can be found elsewhere. 6,15,16,28,30 ■ RESULTS AND DISCUSSION These TT1 molecules exhibit strong aromatic interactions that drive self-assembly.…”

Section: ■ Introductionmentioning

confidence: 99%

Exploration of the Nucleation Pathway for Supramolecular Fibers

Tang

Khatua

Carnevale

et al. 2023

J. Chem. Inf. Model.

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The pathway for supramolecular fiber formation is coupled with the underlying order of the self-assembling molecules. Here, we report on atomistic molecular dynamics simulations to characterize the initial stages of the self-assembly of a model drug amphiphile in an aqueous solution. We perform two-dimensional metadynamics calculations to characterize the assembly space of this model drug amphiphile�Tubustecan, TT1. TT1 is composed of the hydrophobic anticancer drug, Camptothecin (CPT), conjugated to a hydrophilic polyethylene glycol (PEG) chain. We find that the aromatic stacking of CPT drives the formation of a higherdensity liquid droplet. This droplet elongates and can form a higher-ordered supramolecular assembly upon reorganizing and forming an interface and additional aromatic stacking of the drugs. We show that novel reaction coordinates tailored to this class of molecules are essential in capturing the underlying degree of molecular order upon assembly. This approach can be refined and extended to characterize the supramolecular assembly pathway of other molecules containing aromatic compounds.

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Modeling of supramolecular biopolymers: Leading the in silico revolution of tissue engineering and nanomedicine

Fontana

Gelain

2022

Nanotechnology Reviews

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The field of tissue engineering is poised to be positively influenced by the advent of supramolecular biopolymers, because of their promising tailorability coming from the bottom-up approach used for their development, absence of toxic byproducts from their gelation reaction and intrinsic better mimicry of extracellular matrix nanotopography and mechanical properties. However, a deep understanding of the phenomena ruling their properties at the meso- and macroscales is still missing. In silico approaches are increasingly helping to shine a light on questions still of out of reach for almost all empirical methods. In this review, we will present the most significant and updated efforts on molecular modeling of SBP properties, and their interactions with the living counterparts, at all scales. In detail, the currently available molecular mechanic approaches will be discussed, paying attention to the pros and cons related to their representability and transferability. We will also give detailed insights for choosing different biomolecular modeling strategies at various scales. This is a systematic overview of tools and approaches yielding to advances at atomistic, molecular, and supramolecular levels, with a holistic perspective demonstrating the urgent need for theories and models connecting biomaterial design and their biological effect in vivo.

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The interaction of supramolecular anticancer drug amphiphiles with phospholipid membranes

Abstract: The shape of drug delivery vehicles impacts both the circulation time and the effectiveness of the vehicle. Peptide-based drug amphiphiles (DAs) are promising new candidates as drug delivery vehicles that...

Cited by 3 publications

References 75 publications

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Exploration of the Nucleation Pathway for Supramolecular Fibers

Modeling of supramolecular biopolymers: Leading the in silico revolution of tissue engineering and nanomedicine

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