DHDMIQK(KAP): a novel nano-delivery system of dihydroxyl-tetrahydro-isoquinoline-3-carboxylic acid and KPAK towards the thrombus

• DOI: 10.1039/c6tb00874g
• Publication Date: 2016-08-16T08:32:50Z
• Authors: Qiqi Feng; Ming Zhao; Taiping Gan; Haimei Zhu; Yaonan Wang; Shurui Zhao; Yuji Wang; Jianhui Wu; Shiqi Peng
• Keywords: Random hexamer

Vascular thrombosis is a major risk of the onset stroke and so novel therapeutic candidates have been attracting interest. In this context, here docking based computer assisted screening mesoscale simulation were used to design N-[(S)-6,7-dihydroxy-1,1-dimethyl-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]-Lys(Pro-Ala-Lys), DHDMIQK(KAP), for inhibiting P-selectin expression. vitro, 1 nM DHDMIQK(KAP) effectively down-regulated water, in rat plasma solid state formed nanoparticles size capable suitable delivery blood circulation. FT-MS NOESY 2D NMR spectra showed hexamers, identified intermolecular interactions hexamer, assigned hexamer butterfly like conformation. Transmission electron microscopy, scanning microscopy atomic force (AFM) imaged forming size-suitable safe particular, AFM images that adhered onto surfaces platelets. vivo lysed thrombus inhibited with minimal effective dose 0.01 nmol kg-1. spectrum analyses defined specific distribution thrombus, but not vital organs. Therefore, should be nano-delivery system 6,7-dihydroxyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid KPAK target thrombus.