RECEPTOR SPECIFIC ENKEPHALIN ANALOGUES
RECEPTOR SPECIFIC ENKEPHALIN ANALOGUES
批准号:
2263725
负责人:
Victor J Hruby
金额:
$18.56万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1984
资助国家:
美国
项目状态:
已结题
起止时间:
1984-04-01 至 1994-09-30
关键词:
autoradiography behavioral medicine binding proteins brain metabolism chemical structure function conformation drug addiction antagonist drug metabolism drug quality /standard enkephalins guinea pigs hamsters high performance liquid chromatography hormone receptor hormone regulation /control mechanism ion exchange chromatography laboratory mouse laboratory rabbit laboratory rat narcotic antagonists neuropeptide receptor neuropeptides neuropharmacology nuclear magnetic resonance spectroscopy opiate alkaloid peptide analog peptide chemical synthesis protein engineering radiotracer synthetic peptide
中文摘要
我们建议发展一系列旋回和其他构象
英文摘要
We propose to develop a series of cyclic and otherwise conformationally
restricted peptide analogues which have high receptor selectivity, high
agonist or antagonist potency, high stability in vivo, and prolonged
activity for delta and mu opioid receptors. For this purpose, our program
utilizes a multidisciplinary approach combining modern synthetic amino acid
and peptide chemistry, conformational analysis, dynamics, and peptide drug
design, with biochemical, biophysical, physiological, and behavior
pharmacology. Our specific aims include: 1) design, synthesis and
evaluation of novel enkephalin analogues with delta opioid receptor agonist
activity and selectivity; 2) development of delta opioid receptor
antagonists with high selectivity; 3) design, synthesis and evaluation of
cycli, conformationally-constrained somatostatin-like peptides with little
or no somatostatin activity, but with high potency and specificity for mu
opioid receptors; 4) examination in detail of the conformational and
dynamic properties of the most potent and selective analogues from 1, 2,
and 3 to obtain insight into the rational design of more selective or
potent analogues using modern graphics and computational methods; 5) to
examine in detail the binding activities of these compounds at mu and delta
opioid receptors (the most selective analogues with be radiolabeled and
receptor localized in the brain by modern autoradiographic methods); 6) to
obtain a comprehensive evaluation of the opioid agonist and antagonist in
vitro and in vivo activities of the analogues we have prepared and compare
these activities with standard drugs; and 7) to use the above results to
design more specific and more potent analogues for the delta and mu
receptor. The long term goals of this research are to develop an
understanding of the physiological roles of the various opioid receptors,
and to develop ligands for these receptors which can be used for the
treatment of disease.
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Autoradiographic localization of delta opioid receptors in the rat brain using a highly selective bis-penicillamine cyclic enkephalin analog.
使用高选择性双青霉胺环状脑啡肽类似物对大鼠大脑中 δ 阿片受体进行放射自显影定位。
DOI:
10.1016/0014-2999(85)90770-8
发表时间:
1985
期刊:
European journal of pharmacology
影响因子:
5
作者:
[Gulya,K, Gehlert,DR, Wamsley,JK, Mosberg,HI, Hruby,VJ, Duckles,SP, Yamamura,HI]
通讯作者:
Yamamura,HI
Light microscopic autoradiographic localization of delta opioid receptors in the rat brain using a highly selective bis-penicillamine cyclic enkephalin analog.
使用高选择性双青霉胺环状脑啡肽类似物对大鼠大脑中 δ 阿片受体进行光显微放射自显影定位。
DOI:
--
发表时间:
1986
期刊:
The Journal of pharmacology and experimental therapeutics
影响因子:
--
作者:
[Gulya,K, Gehlert,DR, Wamsley,JK, Mosberg,H, Hruby,VJ, Yamamura,HI]
通讯作者:
Yamamura,HI
Opioid peptides: simultaneous delta agonism and mu antagonism in somatostatin analogues.
阿片肽:生长抑素类似物同时具有 δ 激动作用和 mu 拮抗作用。
DOI:
10.1016/s0196-9781(96)00242-2
发表时间:
1997
期刊:
Peptides
影响因子:
3
作者:
[Bonner,GG, Davis,P, Stropova,D, Ferguson,R, Yamamura,HI, Porreca,F, Hruby,VJ]
通讯作者:
Hruby,VJ
Structure-activity analysis of five constrained somatostatin like peptides with opioid antagonist properties.
五种具有阿片拮抗剂特性的受限生长抑素样肽的结构活性分析。
DOI:
--
发表时间:
1987
期刊:
Proceedings of the Western Pharmacology Society
影响因子:
--
作者:
[Wire,WS, Pelton,JT, Kazmierski,W, Hruby,VJ, Burks,TF, Shook,JE]
通讯作者:
Shook,JE
A high affinity, highly selective ligand for the delta opioid receptor: [3H]-[D-Pen2, pCl-Phe4, d-Pen5]enkephalin.
δ 阿片受体的高亲和力、高选择性配体:[3H]-[D-Pen2、pCl-Phe4、d-Pen5]脑啡肽。
DOI:
10.1016/0024-3205(89)90154-9
发表时间:
1989
期刊:
Life sciences
影响因子:
6.1
作者:
[Vaughn,LK, Knapp,RJ, Toth,G, Wan,YP, Hruby,VJ, Yamamura,HI]
通讯作者:
Yamamura,HI
共 12 条
New Modalities for the Treatment of Pain and Drug Abuse
-
批准号:9073233
-
项目类别:
-
资助金额:$53.77万
-
财政年份:2017
-
负责人:Victor J Hruby
-
依托单位:
New Modalities for the Treatment of Pain and Drug Abuse
-
批准号:9918285
-
项目类别:
-
资助金额:$52.92万
-
财政年份:2017
-
负责人:Victor J Hruby
-
依托单位:
Design of Novel Multivalent Ligands with Unique Biological Activity Profiles for Treatment of Prolonged and Neuropathic Pain without Toxicities
-
批准号:9073237
-
项目类别:
-
资助金额:$5.65万
-
财政年份:2017
-
负责人:Victor J Hruby
-
依托单位:
SYNTHESIS CORE
-
批准号:8025973
-
项目类别:
-
资助金额:$16.56万
-
财政年份:2010
-
负责人:Victor J Hruby
-
依托单位:
DESIGN OF NOVEL LIGANDS WITH UNIQUE BIOLOGICAL PROFILES FOR NEUROPATHIC PAIN AND
-
批准号:8025975
-
项目类别:
-
资助金额:$19.82万
-
财政年份:2010
-
负责人:Victor J Hruby
-
依托单位:
ADMINISTRATIVE CORE
-
批准号:8025972
-
项目类别:
-
资助金额:$8.28万
-
财政年份:2010
-
负责人:Victor J Hruby
-
依托单位:
Core - Synthesis Core
-
批准号:7513590
-
项目类别:
-
资助金额:$15.02万
-
财政年份:2007
-
负责人:Victor J Hruby
-
依托单位:
Administrative Core
-
批准号:7513589
-
项目类别:
-
资助金额:$7.15万
-
财政年份:2007
-
负责人:Victor J Hruby
-
依托单位:
Design of Novel Opiod Peptide Ligands With Unique Biological Profiles
-
批准号:7513577
-
项目类别:
-
资助金额:$17.23万
-
财政年份:2007
-
负责人:Victor J Hruby
-
依托单位:
Multimeric Ligands for Targeting Melanoma
-
批准号:8288314
-
项目类别:
-
资助金额:$60.07万
-
财政年份:2003
-
负责人:Victor J Hruby
-
依托单位:
Multimeric Ligands for Targeting Melanoma
-
批准号:8396604
-
项目类别:
-
资助金额:$8.65万
-
财政年份:2003
-
负责人:Victor J Hruby
-
依托单位:
Multimeric Ligands for Targeting Melanoma
-
批准号:8074047
-
项目类别:
-
资助金额:$60.22万
-
财政年份:2003
-
负责人:Victor J Hruby
-
依托单位:
Multimeric Ligands for Targeting Melanoma
-
批准号:8322884
-
项目类别:
-
资助金额:$7.3万
-
财政年份:2003
-
负责人:Victor J Hruby
-
依托单位:
GORDON CONFERENCE ON THE CHEMISTRY AND BIOLOGY OF PEPTID
-
批准号:6460006
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2002
-
负责人:Victor J Hruby
-
依托单位:
Novel Non-Peptide Opioid Ligands for Pain
-
批准号:8416276
-
项目类别:
-
资助金额:$45.81万
-
财政年份:2000
-
负责人:Victor J Hruby
-
依托单位:
NOVEL NON-PEPTIDE OPIOID LIGANDS FOR PAIN
-
批准号:7255810
-
项目类别:
-
资助金额:$45.75万
-
财政年份:2000
-
负责人:Victor J Hruby
-
依托单位:
NOVEL NON-PEPTIDE OPIOID LIGANDS FOR PAIN
-
批准号:6558251
-
项目类别:
-
资助金额:$3.06万
-
财政年份:2000
-
负责人:Victor J Hruby
-
依托单位:
NOVEL NON-PEPTIDE OPIOID LIGANDS FOR PAIN
-
批准号:6189794
-
项目类别:
-
资助金额:$34.09万
-
财政年份:2000
-
负责人:Victor J Hruby
-
依托单位:
NOVEL NON-PEPTIDE OPIOID LIGANDS FOR PAIN
-
批准号:6970137
-
项目类别:
-
资助金额:$42.44万
-
财政年份:2000
-
负责人:Victor J Hruby
-
依托单位:
DESIGN OF OPIOID PEPTIDE LIGANDS AND RECEPTORS
-
批准号:6300718
-
项目类别:
-
资助金额:$10.45万
-
财政年份:2000
-
负责人:Victor J Hruby
-
依托单位:
海外基金