Goode David R, Sharma Anil K, Hergenrother Paul J
Roger Adams Laboratory, University of Illinois, Urbana, IL 61801, USA.
Org Lett. 2005 Aug 4;7(16):3529-32. doi: 10.1021/ol051287d.
Fifteen ketone-containing peptides were designed, synthesized, and used to probe the effect of substitution at the P1' position on caspase-3 and -7 inhibition. Even with the large bias of Ac-Asp-Glu-Val-Asp at the P4-P1 positions, certain peptides with cyclic functionality in the P1' position show a dramatically reduced ability to inhibit these caspases. Additionally, trends toward isozyme selectivity were also uncovered for particular P1' substituents. The data indicate that substitution in the P1' position can drastically affect both caspase inhibition and selectivity. [structure: see text]
设计、合成了15种含酮肽，并用于探究P1'位取代对caspase-3和-7抑制的影响。即使在P4-P1位存在较大的Ac-Asp-Glu-Val-Asp偏向性，某些在P1'位具有环状功能的肽对这些半胱天冬酶的抑制能力也显著降低。此外，还发现了特定P1'取代基的同工酶选择性趋势。数据表明，P1'位的取代可显著影响半胱天冬酶的抑制作用和选择性。[结构：见正文]
