Synthesis and Activity of Novel Kappa Opioid Peptides
新型κ阿片肽的合成及活性
基本信息
- 批准号:6663077
- 负责人:
- 金额:$ 2.24万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-10-01 至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (provided by applicant)
Dynorphin A, an endogenous neuropeptide, is has high affinity and selectivity
for the kappa opioid receptors. It has been reported that the N-terminus
?message? sequence is important for kappa opioid receptor activation while the
?address? sequence is designated as the potency-enhancing domain responsible
for the high specificity of dynorphin A. Two novel lead Dyn A analogues, arodyn
(aromatic dynorphin), and JVA-901, have displayed different structure-activity
relationships from Dyn A. It is therefore hypothesized that arodyn and JVA-901
bind differently to the kappa opioid receptors. The goal of this research
proposal is to identify potent and selective kappa opioid receptor antagonists.
To pursue this goal novel selective kappa receptor antagonists will be designed
utilizing classic and combinatorial peptide libraries and evaluated using
Chinese hamster ovary cells stably expressing opioid receptors. The combination
of classical and combinatorial approaches will be used to modify the sequences
of the two aforementioned lead peptides and generate focused peptide libraries.
Combinatorial peptide libraries offer the advantage of synthesizing a variety
of peptides simultaneously and allows the introduction of various combinations
of amino acids in the sequence of arodyn and JVA-901. Syntheses will be done
using solid phase peptide synthesis. There are many potential clinical
applications of kappa agonists and antagonists, including the prevention of
pancreatitis, neuroprotection (epilepsy) and anti-convulsants, potential
treatment in cocaine abuse and opioid dependence as well as use in
pharmacological assays as pharmacological tools to help understand kappa
receptor-ligand interactions at the molecular level since kappa-selective
peptide antagonists are limited.
描述(由申请人提供)
强啡肽A是一种内源性神经肽,具有高度的亲和力和选择性
对κ阿片受体的影响据报道,N-末端
?留言?序列对于κ阿片受体活化是重要的,而
?地址?序列被指定为负责
强啡肽A的高度特异性两个新的Dyn A类似物arodyn
(芳香强啡肽)和JVA-901显示出不同的结构-活性
关于Dyn A因此,假设arodyn和JVA-901
与κ阿片受体的结合方式不同本研究的目的
本发明的目的是鉴定有效的和选择性的κ阿片样物质受体拮抗剂。
为了实现这一目标,将设计新型选择性κ受体拮抗剂
利用经典的和组合的肽文库,并使用
稳定表达阿片受体的中国仓鼠卵巢细胞。相结合
经典的和组合的方法将被用来修改序列
并产生聚焦的肽文库。
组合肽文库提供了合成多种肽的优点,
并允许引入各种组合
arodyn和JVA-901的序列中的氨基酸序列。将进行合成
使用固相肽合成。有许多潜在的临床
κ激动剂和拮抗剂的应用,包括预防
胰腺炎,神经保护(癫痫)和抗惊厥药,潜在
可卡因滥用和类阿片依赖的治疗以及
作为药理学工具的药理学测定有助于了解kappa
受体-配体相互作用的分子水平,因为κ-选择性
肽拮抗剂是有限的。
项目成果
期刊论文数量(0)
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Synthesis and Activity of Novel Kappa Opioid Peptides
新型κ阿片肽的合成及活性
- 批准号:
6450635 - 财政年份:2001
- 资助金额:
$ 2.24万 - 项目类别: