Title:In Silico Modelling in the Development of Novel Radiolabelled Peptide Probes
Volume: 27
Issue: 41
Author(s): Janke Kleynhans, Hendrik Gerhardus Kruger*, Theunis Cloete, Jan Rijn Zeevaart and Thomas Ebenhan
Affiliation:
- University of KwaZulu Natal, Catalysis and Peptide Research Unit, Durban 4000,South Africa
Keywords:
Computer-aided drug design, Ligand-based drug design, Structure-based drug design, positron emission
tomography (PET), single photon emission tomography (SPECT), Absorption-distribution-metabolism-excretiontoxicity
(ADMET)
Abstract: This review describes the usefulness of in silico design approaches in the design of
new radiopharmaceuticals, especially peptide-based radiotracers (including peptidomimetics).
Although not part of the standard arsenal utilized during radiopharmaceutical design, the use
of in silico strategies is steadily increasing in the field of radiochemistry as it contributes to a
more rational and scientific approach. The development of new peptide-based radiopharmaceuticals
as well as a short introduction to suitable computational approaches are provided in
this review. The first section comprises a concise overview of the three most useful computeraided
drug design strategies used, namely i) a Ligand-based Approach (LBDD) using pharmacophore
modelling, ii) a Structure-based Design Approach (SBDD) using molecular docking
strategies and iii) Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET)
predictions. The second section summarizes the challenges connected to these computer-aided
techniques and discusses successful applications of in silico radiopharmaceutical design in
peptide-based radiopharmaceutical development, thereby improving the clinical procedure in
Nuclear Medicine. Finally, the advances and future potential of in silico modelling as a design
strategy is highlighted.
