从内部数据库中,筛选出以下以半胱氨酸残基为靶点的共价结合分子,这些分子采用如下共价弹头(图1):
- α,β-unsaturated ketones
- α-chloracetamides
- activated acetylenes
- acrylonitriles
- acrylamides
- epoxides
- methyl vinylsulfones
- phenylsulphonate esters
- aminomethyl methyl acrylathes
- primary haloalkanes
这些化合物根据五规则限制进行了预筛选:
- MW 150 - 500
- ClogP -1 - 5
- H-donors 0 - 5
- H-acceptors 0 - 10
- Rotatable bonds ≤ 10
图1. 半胱氨酸靶向共价抑制剂库中化合物的共价弹头分布