苔藓抑素类似物中可调节位点的鉴定：通过后期多样化获得的C20苔藓素

Identification of a tunable site in bryostatin analogs: C20 Bryologs through late stage diversification.

作者信息

Wender Paul A, Baryza Jeremy L

机构信息

Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.

出版信息

Org Lett. 2005 Mar 17;7(6):1177-80. doi: 10.1021/ol0501931.

DOI:10.1021/ol0501931

PMID:15760168

Abstract

[structure: see text] The C20 region of our bryostatin analogs was identified as a nonpharmacophoric site that could be varied to tune analogs for function and physical properties without significantly affecting their binding affinity for PKC. The use of this site in a late-stage diversification strategy has enabled the facile synthesis of a variety of new C20 analogs, all of which retain nanomolar affinity for PKC, in agreement with our pharmacophore hypothesis.

摘要

[结构：见正文] 我们的苔藓抑素类似物的C20区域被确定为一个非药效基团位点，该位点可以改变，以调整类似物的功能和物理性质，而不会显著影响它们对蛋白激酶C（PKC）的结合亲和力。在后期多样化策略中使用该位点能够轻松合成多种新的C20类似物，所有这些类似物对PKC都保持纳摩尔亲和力，这与我们的药效基团假说一致。