caa a22 4500 469053720 CHVBK 20180323132837.0 cr unu---uuuuu 170328e19920401xx s 000 0 eng 10.1007/BF00129424 doi (NATIONALLICENCE)springer-10.1007/BF00129424 In search of new lead compounds for trypanosomiasis drug design: A protein structure-based linked-fragment approach [Elektronische Daten] [Christophe Verlinde, Gabrielle Rudenko, Wim Hol] Summary: A modular method for pursuing structure-based inhibitor design in the framework of a design cycle is presented. The approach entails four stages: (1) a design pathway is defined in the three-dimensional structure of a target protein; (2) this pathway is divided into subregions; (3) complementary building blocks, also called fragments, are designed in each subregion; complementarity is defined in terms of shape, hydrophobicity, hydrogen bond properties and electrostatics; and (4) fragments from different subregions are linked into potential lead compounds. Stages (3) and (4) are qualitatively guided by force-field calculations. In addition, the designed fragments serve as entries for retrieving existing compounds from chemical databases. This linked-fragment approach has been applied in the design of potentially selective inhibitors of triosephosphate isomerase from Trypanosoma brucei, the causative agent of sleeping sickness. ESCOM Science Publishers B.V, 1992 Modular structure-based inhibitor design nationallicence Chemical database nationallicence Triosephosphate isomerase nationallicence Verlinde Christophe BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands aut Rudenko Gabrielle BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands aut Hol Wim BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 6/2(1992-04-01), 131-147 0920-654X 6:2<131 1992 6 10822 https://doi.org/10.1007/BF00129424 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00129424 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Verlinde Christophe BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Rudenko Gabrielle BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Hol Wim BIOSON Research Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 6/2(1992-04-01), 131-147 0920-654X 6:2<131 1992 6 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer