PEPTIDE PROBES OF THE 5HT1A RECEPTOR/G PROTEIN INTERFAC
PEPTIDE PROBES OF THE 5HT1A RECEPTOR/G PROTEIN INTERFAC
批准号:
2883042
负责人:
KEITH Krom PARKER
金额:
$10.54万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1996
资助国家:
美国
项目状态:
已结题
起止时间:
1996-07-01 至 2003-07-31
中文摘要
描述(改编自申请人摘要):
英文摘要
DESCRIPTION (Adapted from applicant's abstract):
Serotonin (5HT) receptors are involved in critical aspects of human health and
disease such as depression and migraine. Our long-term goals are to study the
molecular pharmacology of these receptors, especially interactions between
serotonin receptors and a significant cellular signal transducing scheme, the G
protein system. In the present project, we propose studies with a type of human
serotonin receptor known as the 5HTla receptor. This receptor belongs to a
large superfamily of receptors which include other important model receptors
such as adrenergic, dopaminergic, and muscarinic receptors. Based upon known
properties of these model receptors and serotonin receptors themselves, we have
synthesized and characterized a peptide from a putative G protein coupling
region of the 5HTla receptor. In the present study we will utilize solid phase
methods for synthesizing structural variants of this biologically active
peptide. Activity of variants will be measured using agonist inhibition assays.
Further functional assays will include determinations in changes of the second
messenger cyclic AMP or the enzyme adenylyl cyclase, and by measurement of
guanosine triphosphate (GTP)/ G protein binding. GTP binding assays will be
performed in crude cellular preparations as well as in a cloned G protein
system. Circular dichroism (CD) studies will analyze solution structures of
priority peptides. Information from binding and functional experiments will
contribute to determination of the best peptide tools for key molecular
pharmacology studies of the interface. Advancements is analyzing and modeling
molecular interfaces create a realistic opportunity for discovery of active
conformations of receptor/G protein contact surfaces. Thus selected peptides
will be used as probes of G protein using multi-dimensional nuclear magnetic
resonance (NMR) to better understand the active conformations of the receptor-G
protein interface. Information from our studies will add essential knowledge to
modeling the receptor superfamily. Development of novel therapeutic drugs may
follow.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
Binding properties of dipropyltryptamine at the human 5-HT1a receptor.
二丙基色胺与人类 5-HT1a 受体的结合特性。
DOI:
10.1159/000085649
发表时间:
2005
期刊:
Pharmacology
影响因子:
3.1
作者:
[Thiagaraj,HarishV, Russo,EthanB, Burnett,Andrea, Goldstein,Eric, Thompson,CharlesM, Parker,KeithK]
通讯作者:
Parker,KeithK
MT COBRE: HUMAN 5HT1A RECEPTOR I3 LOOP G PROTEIN INTERFACE STRUCT DETERMINATIONS
-
批准号:7170328
-
项目类别:
-
资助金额:$3.09万
-
财政年份:2005
-
负责人:KEITH Krom PARKER
-
依托单位:
MT COBRE: HUMAN 5HT1A RECEPTOR I3 LOOP G PROTEIN INTERFACE STRUCT DETERMINATIONS
-
批准号:7011766
-
项目类别:
-
资助金额:$11.57万
-
财政年份:2004
-
负责人:KEITH Krom PARKER
-
依托单位:
PEPTIDE PROBES OF THE 5HT1A RECEPTOR G PROTEIN INTERFACE
-
批准号:2828872
-
项目类别:
-
资助金额:$0.92万
-
财政年份:1996
-
负责人:KEITH Krom PARKER
-
依托单位:
PEPTIDE PROBES OF THE 5HT1A RECEPTOR-G PROTEIN INTERFACE
-
批准号:2193684
-
项目类别:
-
资助金额:$9.55万
-
财政年份:1996
-
负责人:KEITH Krom PARKER
-
依托单位:
PEPTIDE PROBES OF THE 5HT1A RECEPTOR-G PROTEIN INTERFACE
-
批准号:2600555
-
项目类别:
-
资助金额:$0.92万
-
财政年份:1996
-
负责人:KEITH Krom PARKER
-
依托单位:
海外基金