Pharmacophore-based small molecule CXCR4 ligands

Tetsuo Narumi; Tomohiro Tanaka; Chie Hashimoto; Wataru Nomura; Haruo Aikawa; Akira Sohma; Kyoko Itotani; Miyako Kawamata; Tsutomu Murakami; Naoki Yamamoto; Hirokazu Tamamura

doi:10.1016/j.bmcl.2012.04.032

Pharmacophore-based small molecule CXCR4 ligands

Bioorg Med Chem Lett. 2012 Jun 15;22(12):4169-72. doi: 10.1016/j.bmcl.2012.04.032. Epub 2012 Apr 20.

Authors

Tetsuo Narumi¹, Tomohiro Tanaka, Chie Hashimoto, Wataru Nomura, Haruo Aikawa, Akira Sohma, Kyoko Itotani, Miyako Kawamata, Tsutomu Murakami, Naoki Yamamoto, Hirokazu Tamamura

Affiliation

¹ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo 101-0062, Japan.

PMID: 22579418
DOI: 10.1016/j.bmcl.2012.04.032

Abstract

Low molecular weight CXCR4 ligands were developed based on the peptide T140, which has previously been identified as a potent CXCR4 antagonist. Some compounds with naphthyl, fluorobenzyl and pyridyl moieties as pharmacophore groups in the molecule showed significant CXCR4-binding activity and anti-HIV activity. Structure-activity relationships were studied and characteristics of each of these three moieties necessary for CXCR4 binding were defined. In this way, CXCR4 ligands with two types of recognition modes for CXCR4 have been found.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / pharmacology
Cell Line
HIV-1 / drug effects
HIV-1 / physiology
Humans
Ligands
Oligopeptides / chemical synthesis*
Oligopeptides / chemistry
Oligopeptides / pharmacology
Receptors, CXCR4 / antagonists & inhibitors*
Receptors, CXCR4 / chemistry
Small Molecule Libraries
Structure-Activity Relationship
T-Lymphocytes / drug effects
T-Lymphocytes / virology
Virus Replication / drug effects

Substances

Anti-HIV Agents
Ligands
Oligopeptides
Receptors, CXCR4
Small Molecule Libraries
T140 peptide