NCAM Mimetic Peptides: An Update
NCAM Mimetic Peptides: An Update
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NCAM 模拟肽：更新
DOI：
10.1007/s11064-008-9771-0
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发表时间：
2008
影响因子：
4.4
通讯作者：
E. Bock
中科院分区：
文献类型：
--
作者：
V. Berezin;E. Bock
神经细胞黏附分子(NCAM)参与与自身以及与其他细胞表面受体和生长因子的多种相对低亲和力的相互作用。它的胞质结构域不具有任何内在的酶活性，这使得开发干扰NCAM功能的可靠药理工具变得困难。最近，我们对NCAM介导的细胞黏附和信号转导的结构基础的了解取得了进展，这使得基于结构的NCAM模拟肽的设计成为可能。利用这种方法，已经鉴定了一些多肽P2，P1-B，P-3-DE和P-3-G，它们的序列包含一个或多个与NCAM本身结合的NCAM同亲结合位点。通过核磁共振滴定分析和分子模拟，已经鉴定了一些从NCAM中提取的靶向NCAM异亲配体的多肽，如成纤维细胞生长因子受体和硫酸乙酰肝素蛋白多糖(HSPG)。FGL、dekaCAM、FRM/EncaminA、BCL、EncaminC和EncaminE均以成纤维细胞生长因子受体为靶标，而肝素结合多肽HBP以HSPG为靶标。此外，通过组合多肽文库的筛选，已经鉴定了一些NCAM结合多肽。C3和NBP10多肽靶向第一Ig模块，而ENFIN2和ENFIN11多肽靶向NCAM的纤维连接蛋白III(FN3)模块。许多NCAM类似物在体外和体内都能诱导神经突起生长并显示出神经保护和突触可塑性调节特性，使它们成为适合于治疗神经退行性疾病和记忆受损的药物开发的有吸引力的药理工具。
The neural cell adhesion molecule (NCAM) is involved in multiple, relatively low affinity interactions with itself and with other cell surface receptors and growth factors. Its cytoplasmic domains do not posses any intrinsic enzymatic activity, which makes it difficult to develop reliable pharmacological tools interfering with NCAM functions. Recent progress in our understanding of the structural basis of NCAM-mediated cell adhesion and signaling has allowed a structure-based design of NCAM mimetic peptides. Using this approach, a number of peptides termed P2, P1-B, P-3-DE and P-3-G, whose sequences contain one or several NCAM homophilic binding sites involved in NCAM binding to itself, have been identified. By means of NMR titration analysis and molecular modeling, a number of peptides derived from NCAM and targeting NCAM heterophilic ligands, such as the fibroblast growth factor receptor and heparan sulfate proteoglycans, (HSPG) have been identified. The FGL, dekaCAM, FRM/EncaminA, BCL, EncaminC and EncaminE peptides, all target the FGF receptor, whereas the heparin-binding peptide HBP targets HSPG. Moreover, a number of NCAM-binding peptides have been identified employing screening of combinatorial peptide libraries. The C3 and NBP10 peptides target the first Ig module, whereas the ENFIN2 and ENFIN11 peptides target fibronectin type III (FN3) modules of NCAM. A number of NCAM mimetics can induce neurite outgrowth and exhibit neuroprotective and synaptic plasticity modulating properties in vitro and in vivo, making them attractive pharmacological tools suitable for drug development for the treatment of neurodegenerative disorders and impaired memory.
影响因子：
5.6
作者：
Schmitt-Ulms, G;Legname, G;Prusiner, SB
通讯作者：
Prusiner, SB