کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10583752 | 981305 | 2014 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
[Dmt1]DALDA analogues with enhanced μ opioid agonist potency and with a mixed μ/κ opioid activity profile
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
FMOC[Dmt1]DALDADSLETPyBOPtert-butyloxycarbonylPBFBOC1,2-ethanediolEDTMVDHOBtEMPTMPTLCDMPRP-HPLCDMTIMPGPi1-hydroxybenzotriazole - 1-هیدروکسی بنزوتریازول9-fluorenylmethoxycarbonyl - 9-فلوئورنیل متیل اکسیدکربنیلDAMGO - DREAMU69,593 - U.69.593imm - انحصارinner mitochondrial membrane - درونی غشای میتوکندریMouse vas deferens - ماوس دفرنسthin layer chromatography - کروماتوگرافی لایه نازکreversed-phase high performance liquid chromatography - کروماتوگرافی مایع با کارایی بالا با فاز برگشت پذیرGuinea pig ileum - گلو خوار ileum
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Analogues of [Dmt1]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt = 2â²,6â²-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity, were prepared by replacing Phe3 with various 2â²,6â²-dialkylated Phe analogues, including 2â²,6â²-dimethylphenylalanine (Dmp), 2â²,4â²,6â²-trimethylphenylalanine (Tmp), 2â²-isopropyl-6â²-methylphenylalanine (Imp) and 2â²-ethyl-6â²-methylphenylalanine (Emp), or with the bulky amino acids 3â²-(1-naphthyl)alanine (1-Nal), 3â²-(2-naphthyl)alanine (2-Nal) or Trp. Several compounds showed significantly increased μ agonist potency, retained μ receptor selectivity and are of interest as drug candidates for neuropathic pain treatment. Surprisingly, the Dmp3-, Imp3-, Emp3- and 1-Nal3-containing analogues showed much increased κ receptor binding affinity and had mixed μ/κ properties. In these cases, molecular dynamics studies indicated conformational preorganization of the unbound peptide ligands due to rotational restriction around the CβCγ bond of the Xxx3 residue, in correlation with the observed κ receptor binding enhancement. Compounds with a mixed μ/κ opioid activity profile are known to have therapeutic potential for treatment of cocaine abuse.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 7, 1 April 2014, Pages 2333-2338
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 7, 1 April 2014, Pages 2333-2338
نویسندگان
Longxiang Bai, Ziyuan Li, Jiajia Chen, Nga N. Chung, Brian C. Wilkes, Tingyou Li, Peter W. Schiller,