Selenoglycosides in silico: ab initio-derived reparameterization of MM4, conformational analysis using histo-blood group ABH antigens and lectin docking as indication for potential of bioactivity
Artikel i vetenskaplig tidskrift, 2010

The identification of glycan epitopes such as the histo-blood group ABH determinants as docking sites for bacterial/viral infections and signals in growth regulation fuels the interest to develop non-hydrolysable mimetics for therapeutic applications. Inevitably, the required substitution of the linkage oxygen atom will alter the derivative's topology. Our study addresses the question of the impact of substitution of oxygen by selenium. In order to characterize spatial parameters and flexibility of selenoglycosides, we first performed ab initio calculations on model compounds to refine the MM4 force field. The following application of the resulting MM4R version appears to reduce the difference to ab initio data when compared to using the MM4 estimator. Systematic conformational searches on the derivatives of histo-blood group ABH antigens revealed increased flexibility with acquisition of additional low-energy conformer(s), akin to the behavior of S-glycosides. Docking analysis using the Glide program for eight test cases indicated potential for bioactivity, giving further experimental investigation a clear direction to testing Se-glycosides as lectin ligands.

mistletoe lectin

solid-phase

binding

Molecular mechanics

Drug design

Selenoglycoside

Lectins

specificities

pseudomonas-aeruginosa

alcohols

ethers

plant

Blood group antigens

genetic algorithm search

force-field

mammalian lectins

Författare

F. Strino

Göteborgs universitet

Biognos AB

J. H. Lii

National Changhua University of Education

Ashok Krishna Chaitanya Koppisetty

Chalmers, Data- och informationsteknik, Datavetenskap

Per-Georg Nyholm

Biognos AB

Göteborgs universitet

H. J. Gabius

Ludwig-Maximilians-Universität München

Journal of Computer-Aided Molecular Design

0920-654X (ISSN) 1573-4951 (eISSN)

Vol. 24 1009-1021

Ämneskategorier

Industriell bioteknik

DOI

10.1007/s10822-010-9392-y