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Niu Huang's Lab


Exploring Halogen Bonds in 5-Hydroxytryptamine 2B Receptor–Ligand Interactions




Novel “pairs” of drugs possessing pharmacological synergies could be encapsulated into polymeric micelles and exert superb therapeutic effects in vivo upon intravenous administration, with the prerequisite that the micelles remain stable. NADP(H) quinone oxidoreductase 1 (NQO1) inhibitors, such as β-lapachone (LPC) and tanshinone IIA (THA) are structurally and pharmacologically similar molecules that are both poorly water soluble, crystallize extremely fast, and demonstrate synergistic anticancer effect when used together with paclitaxel (PTX). However, when co-encapsulated with PTX in poly (ethylene glycol)-b-poly (D, L-lactic acid) (PEG-PLA) micelles, only PTX/LPC but not PTX/THA pair yield satisfactory colloidal stability. To reveal the molecular mechanism contributing to the colloidal stability of the co-encapsulated micelles, we investigated the molecular interactions of PTX/LPC and PTX/THA, through both experimental methods (crystallization kinetics, 13C-NMR) and molecular dynamic simulation. We observed that PTX was capable of inhibiting LPC but not THA crystallization both in aqueous environment and in solid state, which could be attributed to the strong hetero-intermolecular interactions (π-π, H-bonding) between LPC and PTX, which disrupted the homo-intermolecular interactions between LPC molecules and thus formed a favorable miscible binary system. In comparison, the lack of a strong PTX/THA interaction left the strong THA/THA stacking interaction undisturbed and the fast THA crystallization tendency unrestrained. We conclude that the intermolecular interactions, i.e., the “pharmaceutical synergy”, between the co-encapsulated drugs critically control the colloidal stability of polymeric micelles, therefore shall be evaluated when design co-encapsulated drug delivery systems for optimal therapeutic benefits.
Intermolecular interactions between co-encapsulated drugs inhibit drug crystallization and enhance colloidal stability of polymeric micelles.

Classic papers->Medicinal Chemistry

Posted by admin on June 16, 2017
Posted in news 

 Classic papers
Title Author Cited
RA Friesner, RB Murphy, MP Repasky… – Journal of medicinal …, 2006
GL Warren, CW Andrews, AM Capelli… – Journal of medicinal …, 2006
N Huang, BK Shoichet, JJ Irwin – Journal of medicinal chemistry, 2006
W Sherman, T Day, MP Jacobson… – Journal of medicinal …, 2006
J Wang, SM Soisson, K Young, W Shoop, S Kodali… – Nature, 2006
K Ding, Y Lu, Z Nikolovska-Coleska… – Journal of medicinal …, 2006
M Matsumoto, H Hashizume, T Tomishige… – PLoS Med, 2006
No profilesNo profiles
HA Overton, AJ Babbs, SM Doel, MCT Fyfe… – Cell …, 2006
No profilesNo profiles
MS Karthikeyan, DJ Prasad, B Poojary… – … & medicinal chemistry, 2006
M Whiting, J Muldoon, YC Lin… – Angewandte Chemie …, 2006
Dates and citation counts are estimated and are determined automatically by a computer program.

CryoEM structure of yeast cytoplasmic exosome complex.

Posted by admin on December 12, 2016
Posted in news 

CryoEM structure of yeast cytoplasmic exosome complex.

Jun-Jie Liu1,2,*, Chu-Ya Niu1,*, Yao Wu3,*, Dan Tan3, Yang Wang1, Ming-Da Ye1, Yang Liu2,4, Wenwei Zhao4, Ke Zhou5, Quan-Sheng Liu5, Junbiao Dai6, Xuerui Yang4, Meng-Qiu Dong3, Niu Huang3 and Hong-Wei Wang1