Counting on Fragment Based Drug Design Approach for Drug Discovery

被引:26
作者
Kashyap, Aanchal [1 ]
Singh, Pankaj Kumar [1 ]
Silakari, Om [1 ]
机构
[1] Punjabi Univ, MML, Dept Pharmaceut Sci & Drug Res, Patiala 147002, Punjab, India
关键词
Drug discovery; FBDD; NMR; X-ray crystallography; CADD; HTS; DE-NOVO DESIGN; INHIBITORS; IDENTIFICATION; METHYLTRANSFERASE; MODULATORS; RECEPTOR; LIGANDS;
D O I
10.2174/1568026619666181130134250
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Fragment Based Drug Design (FBDD) is a structure guided ligand design approach used in the process of drug discovery. It involves identification of low molecular weight fragments as hits followed by determination of their binding mode using X-ray crystallography and/or NMR spectroscopy. X-ray protein crystallography is one of the most sensitive biophysical methods used for screening and is least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. The retrieved binding information facilitates the optimization of fragments into drug like molecules. These identified molecules bind efficiently with the target proteins and form high quality binding interactions. Fragment-based screening using X-ray crystallography is, therefore, an efficient method for identifying binding hotspots on proteins that can be further exploited by chemists and biologists for the discovery of new drugs. The recent advancements in FBDD technique are illustrated in this review along with recently published success stories of FBDD technique in drug discovery.
引用
收藏
页码:2284 / 2293
页数:10
相关论文
共 52 条
  • [1] Application of Fragment-Based Screening to the Design of Inhibitors of Escherichia coli DsbA
    Adams, Luke A.
    Sharma, Pooja
    Mohanty, Biswaranjan
    Ilyichova, Olga V.
    Mulcair, Mark D.
    Williams, Martin L.
    Gleeson, Ellen C.
    Totsika, Makrina
    Doak, Bradley C.
    Caria, Sofia
    Rimmer, Kieran
    Horne, James
    Shouldice, Stephen R.
    Vazirani, Mansha
    Headey, Stephen J.
    Plumb, Brent R.
    Martin, Jennifer L.
    Heras, Begona
    Simpson, Jamie S.
    Scanlon, Martin J.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2015, 54 (07) : 2179 - 2184
  • [2] Fragment-based discovery of a new family of non-peptidic small-molecule cyclophilin inhibitors with potent antiviral activities
    Ahmed-Belkacem, Abdelhakim
    Colliandre, Lionel
    Ahnou, Nazim
    Nevers, Quentin
    Gelin, Muriel
    Bessin, Yannick
    Brillet, Rozenn
    Cala, Olivier
    Douguet, Dominique
    Bourguet, William
    Krimm, Isabelle
    Pawlotsky, Jean-Michel
    Guichou, Jean-Francois
    [J]. NATURE COMMUNICATIONS, 2016, 7
  • [3] Discovery of Novel Pneumococcal Surface Antigen A (PsaA) Inhibitors Using a Fragment-based Drug Design Approach
    Bajaj, Megha
    Mamidyala, Sreeman K.
    Zuegg, Johannes
    Begg, Stephanie L.
    Ween, Miranda P.
    Luo, Zhenyao
    Huang, Johnny X.
    McEwan, Alastair G.
    Kobe, Bostjan
    Paton, James C.
    McDevitt, Christopher A.
    Cooper, Matthew A.
    [J]. ACS CHEMICAL BIOLOGY, 2015, 10 (06) : 1511 - 1520
  • [4] Discovery of novel dengue virus NS5 methyltransferase non-nucleoside inhibitors by fragment-based drug design
    Benmansour, Fatiha
    Trist, Iuni
    Coutard, Bruno
    Decroly, Etienne
    Querat, Gilles
    Brancale, Andrea
    Barral, Karine
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 125 : 865 - 880
  • [5] Structure of the σ1 Receptor and Its Ligand Binding Site Miniperspective
    Brune, Stefanie
    Pricl, Sabrina
    Wuensch, Bernhard
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (24) : 9809 - 9819
  • [6] Discovery of Tricyclic Indoles That Potently Inhibit Mcl-1 Using Fragment-Based Methods and Structure-Based Design
    Burke, Jason P.
    Bian, Zhiguo
    Shaw, Subrata
    Zhao, Bin
    Goodwin, Craig M.
    Belmar, Johannes
    Browning, Carrie F.
    Vigil, Dominico
    Friberg, Anders
    Camper, DeMarco V.
    Rossanese, Olivia W.
    Lee, Taekyu
    Olejniczak, Edward T.
    Fesik, Stephen W.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (09) : 3794 - 3805
  • [7] In Silico Fragment-Based Design Identifies Subfamily B1 Metallo-β-lactamase Inhibitors
    Cain, Ricky
    Brem, Jurgen
    Zollman, David
    McDonough, Michael A.
    Johnson, Rachel M.
    Spencer, James
    Makena, Anne
    Abboud, Martine I.
    Cahill, Samuel
    Lee, Sook Y.
    McHugh, Peter J.
    Schofield, Christopher J.
    Fishwick, Colin W. G.
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (03) : 1255 - 1260
  • [8] Capelli AM, 2012, PHARM PAT ANAL, V1, P469, DOI [10.4155/ppa.12.46, 10.4155/PPA.12.46]
  • [9] Predicting Allosteric Effects from Orthosteric Binding in Hsp90-Ligand Interactions: Implications for Fragment-Based Drug Design
    Chandramohan, Arun
    Krishnamurthy, Srinath
    Larsson, Andreas
    Nordlund, Paer
    Jansson, Anna
    Anand, Ganesh S.
    [J]. PLOS COMPUTATIONAL BIOLOGY, 2016, 12 (06)
  • [10] Chang L., 2017, MOJ BIOEQUIV AVAILAB, V4