202410-99-9Relevant academic research and scientific papers
DHDMIQK(KAP): A novel nano-delivery system of dihydroxyl-tetrahydro-isoquinoline-3-carboxylic acid and KPAK towards the thrombus
Feng, Qiqi,Zhao, Ming,Gan, Taiping,Zhu, Haimei,Wang, Yaonan,Zhao, Shurui,Wang, Yuji,Wu, Jianhui,Peng, Shiqi
, p. 5991 - 6003 (2016)
Vascular thrombosis is a major risk of the onset of stroke and so novel therapeutic candidates have been attracting interest. In this context, here docking based computer assisted screening and 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. In vitro, 1 nM of DHDMIQK(KAP) effectively down-regulated P-selectin expression. In water, in rat plasma and in the solid state DHDMIQK(KAP) formed nanoparticles of a size capable of suitable delivery in the blood circulation. FT-MS and NOESY 2D NMR spectra showed DHDMIQK(KAP) formed hexamers, identified the intermolecular interactions of the hexamer, and assigned the hexamer a butterfly like conformation. Transmission electron microscopy, scanning electron microscopy and atomic force microscopy (AFM) imaged DHDMIQK(KAP) forming size-suitable nanoparticles for safe delivery in the blood circulation. In particular, AFM images showed that the nanoparticles effectively adhered onto the surfaces of the platelets. In vivo DHDMIQK(KAP) lysed the thrombus and inhibited thrombosis with a minimal effective dose of 0.01 nmol kg-1. FT-MS spectrum analyses defined a specific distribution of DHDMIQK(KAP) in the thrombus, but not in the blood and vital organs. Therefore, DHDMIQK(KAP) should be a novel nano-delivery system of 6,7-dihydroxyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and KPAK to target the thrombus.
NEW COMPOUNDS HAVING TRIPLE ACTIVITIES OF THROMBOLYSIS, ANTITHROMBOTIC AND RADICAL SCAVENGING, AND SYNTHESIS, NANO-STRUCTURE AND USE THEREOF
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Paragraph 0086; 0111, (2016/04/19)
The present invention relates to a compound simultaneously having triple activities of thrombolysis, antithrombosis and free radical scavenging, as well as the preparation method, composition, and applications thereof. The compound is represented by the f
NOVEL COMPOUND WITH EFFECTS OF THROMBOLYSIS, FREE RADICAL SCAVENGING AND THROMBUS-TARGETING AS WELL AS PREPARATION METHOD AND USE THEREOF
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, (2015/11/03)
The present invention discloses a novel compound with effects of thrombolysis, free radical scavenging and thrombus-targeting, as well as a preparation method and use thereof. The compound is a ternary conjugate formed by conjugating a thrombolytic peptide, a free radical scavenger and a thrombus-targeting/antithrombotic peptide together via a linking arm. The present invention also discloses a pharmaceutical composition containing the compounds, wherein the compounds form a nanospherical structure.
A new class of β-carboline alkaloid-peptide conjugates with therapeutic efficacy in acute limb ischemia/reperfusion injury
Bi, Wei,Bi, Yue,Xue, Ping,Zhang, Yanrong,Gao, Xiang,Wang, Zhibo,Li, Meng,Baudy-Floc'H, Michle,Ngerebara, Nathaniel,Michael Gibson,Bi, Lanrong
, p. 1453 - 1462 (2011/05/06)
We describe a novel class of β-carboline alkaloid-peptide conjugates that possess both free radical scavenging and thrombolytic activity. These conjugates demonstrate therapeutic efficacy in a rat arterial thrombosis assay, as well as free radical scavenging capacity as evaluated in a PC12 cell survival assay. Our results indicate that β-carboline alkaloid-peptide conjugate 26a exerts a significant protective effect against local and remote organ injury induced by limb I/R injury in the rat.
Synthesis and biological activity of nitronyl nitroxide containing peptides
Zhao, Ming,Liu, Junling,Wang, Chao,Wang, Lili,Liu, Hu,Peng, Shiqi
, p. 4285 - 4292 (2007/10/03)
[1-(1′,3′-Dioxyl-4′,4′,5′, 5′-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1′,3′-dioxyl- 4′,4′,5′,5′-tetramethyldihydroimidazol-2-yl) -phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9c was evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.
The composition and sequence specificity of Pro-Ala-Lys-OH for the thrombolytic activities of P6A and related oligopeptides
Zhao, Ming,Wang, Chao,Liu, Jiangyuan,Zhou, Kexiang,Peng, Shiqi
, p. 2275 - 2286 (2007/10/03)
The in vitro and in vivo thrombolytic activities of Ala-Arg-Pro-Ala-Lys-OH, its analogs and the related peptides were assayed. The results indicate that when 5Lys of Ala-Arg-Pro-Ala-Lys-OH is changed into 5Arg, and 3Lys of
Identification, synthesis and bioassay for the metabolites of P6A
Zhao, Ming,Wang, Chao,Yang, Jian,Liu, Jiangyuan,Xu, Youxuan,Wu, Yanfen,Peng, Shiqi
, p. 4913 - 4920 (2007/10/03)
The metabolites Ala-Arg-Pro-Ala-OH, Ala-Arg-Pro-OH, Arg-Pro-Ala-Lys-OH and Pro-Ala-Lys-OH were identified by HPLC/ESI/MS from the in vivo blood of Ala-Arg-Pro-Ala-Lys-OH (P6A) received mice. The in vitro incubation of P6A in the blood of mice the same met
Studies on Hybrid Peptides of Fragments from Fibrinogen
Zhao, Ming,Peng, Shiqi
, p. 668 - 676 (2007/10/03)
In the present paper the hybrid peptides of P6A and RGD, namely ARPAKRGDS 17, ARPAKRGDV19, ARPAKRGDF 21, QRPAKRGDS 18, QRPAKRGDV 20 and QRPAKRGDF 22, were synthesized via the solution method, segment condensation and TFA/TFMS A-catalyzed deprotection (in
