Recently, it was reported that tetrapeptides cyclized via lactam bond between the amino terminus and a glutamic residue in position 4 (termed here N-lock) can nucleate helix formation in longer peptides. We applied such strategy to derive N-locked covalent BH3 peptides that were designed to selectively target the anti-apoptotic protein Bfl-1. The resulting agents were soluble in aqueous buffer and displayed a remarkable (low nanomolar) affinity for Bfl-1 and cellular activity. The crystal structure of the complex between such N-locked covalent peptide and Bfl-1 provided insights on the geometry of the N-locking strategy and of the covalent bond between the agent and Bfl-1.

中文翻译：

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共价螺旋肽的N锁稳定作用：应用于Bfl-1拮抗剂。

最近，据报道，通过氨基末端和位置4的谷氨酸残基之间的内酰胺键环化的四肽（在此称为N-锁）可以使更长的肽中的螺旋形成成核。我们应用这种策略来衍生N锁的共价BH3肽，旨在选择性地靶向抗凋亡蛋白Bfl-1。所得试剂可溶于水性缓冲液，并显示出对Bfl-1和细胞活性的显着（低纳摩尔）亲和力。这种N-锁定的共价肽和Bfl-1之间的复合物的晶体结构提供了关于N-锁定策略的几何形状以及试剂与Bfl-1之间的共价键的见解。