Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain.
Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain; Departament de Química Orgànica, Universitat de Barcelona, Martí i Franqués, 1-11, 08028 Barcelona, Spain.
Bioorg Med Chem Lett. 2014 Jan 1;24(1):103-7. doi: 10.1016/j.bmcl.2013.11.065. Epub 2013 Dec 3.
We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization between allylGly 3 and 14 proceeded in moderate yield, excellent cyclic/linear ratio and very high Z-double bond selectivity. NMR studies also demonstrated that the conformational flexibility of this peptide is increased in comparison to that of the natural hormone. Remarkably, this alkene-bridged somatostatin analog is highly selective against somatostatin receptors 1 and 5, suggesting that conformational rigidity is not required for the efficient interaction of somatostatin analogues with these two receptors.
我们在这里描述了第一个十四肽生长抑素类似物，其中二硫键已被碳-碳双键取代。该类似物是使用微波辅助的环 closing metathesis（RCM）反应，使用第二代 Grubbs 作为催化剂制备的。在我们优化的条件下，烯丙基 Gly 3 和 14 之间的环化反应以中等产率、极好的环状/线状比例和非常高的 Z-双键选择性进行。NMR 研究还表明，与天然激素相比，该肽的构象灵活性增加。值得注意的是，这种烯键桥连的生长抑素类似物对生长抑素受体 1 和 5 具有高度选择性，表明构象刚性不是生长抑素类似物与这两种受体有效相互作用所必需的。
