Javascript must be enabled for the correct page display

Approaches to Fragment-Based Drug Design, A comparison between fragment optimization methods

Bonnema, Hotze (2022) Approaches to Fragment-Based Drug Design, A comparison between fragment optimization methods. Bachelor's Thesis, Pharmacy.

[img]
Preview
Text
FBDD, comparison of fragment optimization approaches.pdf

Download (912kB) | Preview
[img] Text
toestemming.pdf
Restricted to Registered users only

Download (119kB)

Abstract

High Throughput Screening (HTS) has discovered a wide range of new chemical entities. However, with the exponentially increasing costs for drug development the industry is highly interested in alternative methods with lower costs. Over the past decades, Fragment-Based Drug Design (FBDD), which performs research on low molecular-weight molecules, has obtained this interest. Interestingly enough, this yielded a higher hit rate, higher binding efficiency & lower costs compared to the traditional HTS. Selected high-affinity fragments serve as great starting points for fragment optimization, a process that increases its size in the pursuit of higher potency. This study aimed to compare the widely used fragment growing and linking approaches and determine their potential for FBDD (1) (2). After successfully comparing and assessing both optimization approaches for FBDD the following has been concluded. • The fragment growing approach provides the most consistent results and is applicable for a wide range of targets. The precise alterations allow for a versatile exploration of the chemical space inside the target’s binding pocket. • The fragment linking approach contains a lot of potential and alterations to rapidly improve the binding affinity of fragments. Because of this potential, this optimization technique should always be taken into consideration. • It is recommended to develop guidelines for the fragment optimization selection process to allow the suitability of each strategy

Item Type: Thesis (Bachelor's Thesis)
Supervisor name: Groves, M.R.
Degree programme: Pharmacy
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 19 Apr 2022 09:58
Last Modified: 19 Apr 2022 09:58
URI: https://fse.studenttheses.ub.rug.nl/id/eprint/26914

Actions (login required)

View Item View Item