Novel analogs of VIP with multiple C-terminal domains

详细信息	查看全文 | 推荐本文 |

• 作者：David Dangoor ; Sara Rubinraut ; Mati Fridkin ; Illana Gozes
• 关键词：VIP ; VPAC1 ; cAMP ; HT-29 cells ; Peptides ; Receptor binding
• 刊名：Peptides
• 出版年：2007
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：September 2007
• 卷：28
• 期：9
• 页码：1622-1630
• 文件大小：534 K

摘要

The effect of multiplication of the N-terminal domain of vasoactive intestinal peptide (VIP) on the binding activity of the peptide was recently evaluated. A VIP analog with multiple N-terminal domains was found to be slightly more potent as compared to [Nle¹⁷]VIP towards VIP receptor type 1 (VPAC1)—related cAMP production. Here, the effect of multiplication of the C-terminal domain of VIP was evaluated with the aim of possibly amplifying peptide-receptor (VPAC1) binding and activation. Several VIP analogs were designed and synthesized, each carrying multiplication of the C-terminal domain that was obtained by either a simple linear tandem extension or by a unique branching methodology. Results show that despite significant alterations in the C-terminal domain of VIP that is considered essential to induce potent receptor binding, few peptides demonstrated only slight reduction in receptor binding and activation in comparison to [Nle¹⁷]VIP. Furthermore, a specific branched VIP analog with multiple C-terminal domains was equipotent to [Nle¹⁷]VIP in the cAMP production assay. Therefore, it is concluded that the association between the VIP ligand to the VIP receptor could be tolerable to size increases in the C-terminal region of the VIP ligand and multiplication of the C-terminal does not increase activity.