ETD

• albumin binding
• apelin receptor
• peptide therapeutics
• pharmacokinetics
• solid-phase peptide synthesis
• theranostics
• transhtyretin binding

Nowadays, cancer remains one of the leading causes of death worldwide. Traditional therapies are associated with severe side effects and limited efficacy, while diagnostic techniques have limited sensitivity.
Given the need to develop more selective and sensitive diagnostic and therapeutic strategies, radiolabelled peptides have emerged as promising agents due to their ability to target tumour-associated receptors selectively. However, their clinical application is limited by their short in vivo half-life, because of rapid plasma degradation and clearance.
This project focused on the design and synthesis of peptide analogues for theranostic applications, aiming to extend their half-life through plasma protein-binding strategies involving transthyretin and serum albumin.
An apelin analogue was synthesised via Fmoc-based solid-phase peptide synthesis (SPPS) and functionalised with a PEG linker, a diflunisal derivative to promote TTR binding, and the chelator DOTA.
In parallel, an alternative strategy was developed by synthesising via SPPS and conjugating an EYE peptide motif with palmitic acid and Mambaquaretin to enhance albumin binding.
All compounds were characterised by LC-MS, HPLC, UV, and MALDI-TOF, and biologically evaluated.