Molecular design opportunities presented by solvent-exposed regions of target proteins

被引：34

作者：

Jiang, Xiangyi ^{[1
]}

Yu, Ji ^{[1
]}

Zhou, Zhongxia ^{[1
]}

Kongsted, Jacob ^{[2
]}

Song, Yuning ^{[3
]}

Pannecouque, Christophe ^{[4
]}

De Clercq, Erik ^{[4
]}

Kang, Dongwei ^{[1
]}

Poongavanam, Vasanthanathan ^{[2
,5
]}

Liu, Xinyong ^{[1
]}

Zhan, Peng ^{[1
]}

机构：

[1] Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, Key Lab Chem Biol,Minist Educ, 44 West Culture Rd, Jinan 250012, Shandong, Peoples R China

[2] Univ Southern Denmark, Dept Phys Chem & Pharm, DK-5230 Odense M, Denmark

[3] Shandong Univ, Dept Clin Pharm, Qilu Hosp, Jinan, Shandong, Peoples R China

[4] Rega Inst Med Res, Lab Virol & Chemotherapy, Leuven, Belgium

[5] Uppsala Univ, Biomedicinskt Ctr BMC, Dept Chem, Husargatan 3, S-75237 Uppsala, Sweden

来源：

MEDICINAL RESEARCH REVIEWS | 2019年 / 39卷 / 06期

基金：

中国国家自然科学基金;

关键词：

drug design; medicinal chemistry; protein; solvent interface; solvent-accessible region; solvent-exposed region; solvent-filled pocket; HIV-1; REVERSE-TRANSCRIPTASE; STRUCTURE-BASED OPTIMIZATION; ANAPLASTIC LYMPHOMA KINASE; FRAGMENT-BASED DISCOVERY; STRUCTURE-GUIDED DESIGN; NITRIC-OXIDE SYNTHASE; HISTONE DEACETYLASE; DUAL INHIBITORS; BIOLOGICAL EVALUATION; DRUG DISCOVERY;

D O I：

10.1002/med.21581

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Solvent-exposed regions, or solvent-filled pockets, within or adjacent to the ligand-binding sites of drug-target proteins provide opportunities for substantial modifications of existing small-molecular drug molecules without serious loss of activity. In this review, we present recent selected examples of exploitation of solvent-exposed regions of proteins in drug design and development from the recent medicinal-chemistry literature.

引用

页码：2194 / 2238

页数：45

共 22 条

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VERHOEVEN, JW
VERHOEVENSCHOFFAM, A
MASSON, A
SCHWYZER, R
HELVETICA CHIMICA ACTA, 1974, 57 (08) : 2503 - 2514
[22] Molecular modeling based design of novel anticancer therapeutics that target the active sites of polymorphic GSTP1 proteins.
Ali-Osman, F
Buolanwini, J
CLINICAL CANCER RESEARCH, 1999, 5 : 3841S - 3841S

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