Synthesis and in vitro bioactivity of human growth hormone-releasing factor analogs substituted at position-1.
Synthesis and in vitro bioactivity of human growth hormone-releasing factor analogs substituted at position-1.
复制标题
DOI：
10.1016/0006-291x(84)90475-3
复制
发表时间：
1984-07
影响因子：
3.1
通讯作者：
N. Ling;A. Baird;W. Wehrenberg;N. Ueno;T. Munegumi;T. Chiang;M. Regno;P. Brazeau
中科院分区：
文献类型：
--
作者：
N. Ling;A. Baird;W. Wehrenberg;N. Ueno;T. Munegumi;T. Chiang;M. Regno;P. Brazeau
用固相法合成了8个40-氨基酸片段的1位类似物和2个人生长激素释放因子的1位类似物，并用单层培养的大鼠垂体前叶细胞测定其释放生长激素的能力。相对于任意指定为1的效力值的hGRF（1-40）OH，[D-Tyr 1]hGRF（1-40）OH、[Phe 1]hGRF（1 - 40）OH、[Trp 1]hGRF（1 - 40）OH、[His 1]hGRF（1 - 40）OH、[Ala 1]hGRF（1-40）OH、[（N-Ac）Tyr 1]hGRF（1-40）OH、Arg 0-hGRF（1-40）OH和Ala 0-hGRF（1-40）OH具有0.022的效力，0.038、0.003、0.351、0.010、0.032、0.002和0.007。相对于hGRF（1-44）NH 2 = 1，[（3-Me）His 1]hGRF（1-44）NH 2和[[O-Me）Tyr 1]hGRF（1-44）NH 2的效价分别为0.132和0.001。这些结果证明了在位置-1处的芳香族残基对于有效生物活性的先决条件，并且还表明与第一个残基形成氢键的能力是完全受体-配体相互作用所需的。
Eight position-1 analogs of the 40-amino acid fragment and two position-1 analogs of human growth hormone-releasing factor were synthesized by solid phase methodology and their capacity to release growth hormone was determined using rat anterior pituitary cells in monolayer culture. Relative to hGRF(1–40)OH, which was arbitrarily assigned a potency value of 1, [D-Tyr1]hGRF(1–40)OH, [Phe1]hGRF(1–40)OH, [Trp1]hGRF(1–40)OH, [His1]hGRF(1–40)OH, [Ala1]hGRF(1–40)OH, [(N-Ac)Tyr1]hGRF(1–40)OH, Arg0-hGRF(1–40)OH and Ala0-hGRF(1–40)OH have potencies of 0.022, 0.038, 0.003, 0.351, 0.010, 0.032, 0.002 and 0.007 respectively. Relative to hGRF(1–44)NH2= 1, [(3-Me)His1]hGRF(1–44)NH2and [[O-Me)Tyr1]hGRF(1–44)NH2have potiencies of 0.132 and 0.001 respectively. These results demonstrate the prerequisite for an aromatic residue at position-1 for potent biological activity and also suggest that the capacity for hydrogen bond formation with the first residue is required for full receptor-ligand interaction.