Structure-activity relationship studies for the peptide portion of the bladder epithelial cell antiproliferative factor from interstitial cystitis patients.
Structure-activity relationship studies for the peptide portion of the bladder epithelial cell antiproliferative factor from interstitial cystitis patients.
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DOI：
10.1021/jm8002763
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发表时间：
2008-10-09
影响因子：
7.3
通讯作者：
Michejda CJ
中科院分区：
文献类型：
--
作者：
Kaczmarek P;Keay SK;Tocci GM;Koch KR;Zhang CO;Barchi JJ Jr;Grkovic D;Guo L;Michejda CJ
我们对抗增殖因子(APF)的多肽部分进行了全面的构效关系(SAR)研究，APF是一种唾液酸化的卷曲-8相关糖肽，可抑制正常膀胱上皮和尿路上皮癌细胞的增殖。采用标准Fmoc化学方法固相合成糖肽衍生物，用反相高效液相色谱法进行纯化，中间产物和最终产物均经高效液相色谱-质谱仪和核磁共振分析确证。通过抑制人原代正常膀胱上皮细胞的~3H-胸腺嘧啶核苷掺入来检测其抗增殖活性。对生物活性有重要影响的APF多肽片段的结构成分包括9个N端氨基酸中的至少8个、C端氨基酸中的负电荷、N端的游离氨基、C端尾的特定氨基酸序列的维持以及多肽键的反式构象。这些数据为设计APF类似物作为潜在的治疗剂时的结构优化提供了重要的指导方针。
We performed comprehensive structure–activity relationship (SAR) studies on the peptide portion of antiproliferative factor (APF), a sialylated frizzled-8 related glycopeptide that inhibits normal bladder epithelial and urothelial carcinoma cell proliferation. Glycopeptide derivatives were synthesized by solid-phase methods using standard Fmoc chemistry and purified by RP-HPLC; all intermediate and final products were verified by HPLC-MS and NMR analyses. Antiproliferative activity of each derivative was determined by inhibition of 3H-thymidine incorporation in primary normal human bladder epithelial cells. Structural components of the peptide segment of APF that proved to be important for biological activity included the presence of at least eight of the nine N-terminal amino acids, a negative charge in the C-terminal amino acid, a free amino group at the N-terminus, maintenance of a specific amino acid sequence in the C-terminal tail, and trans conformation for the peptide bonds. These data provide critical guidelines for optimization of structure in design of APF analogues as potential therapeutic agents.
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影响因子：
5.6
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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DOI：
10.1073/pnas.0404509101
发表时间：
2004-08-10
影响因子：
11.1
作者：
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通讯作者：
Michejda, CJ