Development of a novel PKC ligand using machine learning model: synthesis and PKC surrogate binding of the simplified analogues of alotaketals

Jumpei Maki; Asami Oshimura; Chihiro Tsukano; Ryo Yanagita; Yutaka Saito; Yasubumi Sakakibara; Kazuhiro Irie

doi:10.26434/chemrxiv-2022-fnqnj

Organic Chemistry

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Development of a novel PKC ligand using machine learning model: synthesis and PKC surrogate binding of the simplified analogues of alotaketals

Working Paper

Jumpei Maki Kyoto University ,
Asami Oshimura Kyoto University ,
Chihiro Tsukano Kyoto University ,
Ryo Yanagita Kagawa University ,
Yutaka Saito Waseda University & National Institute of Advanced Industrial Science and Technology ,
Yasubumi Sakakibara Keio University ,
Kazuhiro Irie Kyoto University

Abstract

We have designed and synthesized a new PKC ligand with a novel skeleton based on alotaketals through in silico screening, docking analysis, and molecular dynamics simulation. We found that the new ligand has a higher affinity for PKCα-C1A than for PKCδ-C1B. This compound is expected to serve as the basis for developing PKC ligands with isozyme selectivity.