{"id":145572,"date":"2026-07-01T09:00:04","date_gmt":"2026-07-01T01:00:04","guid":{"rendered":"https:\/\/www.curtin.edu.au\/research\/?post_type=hdr-r-projects&p=145572"},"modified":"2026-07-01T09:00:10","modified_gmt":"2026-07-01T01:00:10","slug":"tailoring-peptide-phage-display-libraries-towards-challenging-drug-targets-through-chemical-modification","status":"publish","type":"hdr-r-projects","link":"https:\/\/www.curtin.edu.au\/research\/hdr-r-projects\/tailoring-peptide-phage-display-libraries-towards-challenging-drug-targets-through-chemical-modification\/","title":{"rendered":"Tailoring peptide phage display libraries towards challenging drug targets through chemical modification"},"content":{"rendered":"\n
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Discovery of new inhibitors against potential drug targets is challenging, especially for so called \u201cundruggable\u201d targets. Compared to conventional small molecules, peptides represent a more suitable drug modality for targeting these types of proteins, with peptide phage display technologies providing a convenient means for discovery of new inhibitors.
Various chemical cyclisation strategies have been employed on phage displayed peptides for screening a range of cyclic peptide libraries against proteins. These include functionalised linkers, incorporation of fragments and unnatural amino acids, and covalent warheads for targeting reactive residues such as Cys. Screening these chemically modified peptide phage display libraries have previously been tested as proof-of-concept, but there remains potential for streamlined targeting.
This medicinal chemistry project will explore chemical modification of peptides on phage display libraries for tailored targeting of challenging cancer drug targets.<\/p>\n\n\n\n


Aim\u00a0\u00a0<\/p>\n\n\n\n

The overall aim of this project is to develop a platform that allows incorporation of interchangeable functional linkers, functional handles, and reactive warheads to suit the protein drug target. These functional handles will be applicable to downstream biological evaluation. This project will be made up of three main aims with opportunities to tailor the project to the candidates\u2019 interests for any or all of the aims:<\/p>\n\n\n\n

    \n
  1. Diversifying chemical cyclisation strategies for peptides in phage display screening<\/li>\n\n\n\n
  2. Screening challenging cancer-related protein targets in tailored phage display libraries<\/li>\n\n\n\n
  3. Biological evaluation of newly discovered inhibitors towards potential cancer therapeutics<\/li>\n<\/ol>\n\n\n\n


    Objectives\u00a0<\/p>\n\n\n\n

    Aim 1: New linkers will be designed and synthesised for cyclising peptides in phage display. Peptides will be cyclised using reimagined cyclisation strategies that incorporate various functionalities such as covalent warheads. New linkers will be tested on model peptides and in phage libraries.

    Aim 2: Using newly designed phage display libraries, new protein targets will be screened to identify new peptide inhibitors, focusing on cancer drug targets that lack known or effective inhibitors. Biopanning conditions will be optimised for the new cyclisation strategies.

    Aim 3: Top peptide hits will be synthesised, analysed for target binding, and tested in various cellular assays. Top peptides will undergo further optimisation to generate potential lead compounds.<\/p>\n\n\n\n


    Significance\u00a0<\/p>\n\n\n\n

    New chemical methods which allow incorporation of a range of reactive moieties onto peptides during phage display will diversify our screening capabilities. These tailored libraries will enhance the inhibitor discovery process for a range of cancer protein targets, particularly those considered challenging or difficult to drug. These methods will be used to screen new protein targets involved in cancer progression for inhibitor discovery and development towards potential new drug candidates, with a focus on hard-to-treat cancers or those that currently lack effective therapies.<\/p>\n\n\n\n


    Ideal Candidate\u00a0<\/p>\n\n\n\n

    We are looking for a PhD candidate with excellent attention to detail, problem-solving skills, and a desire to learn new skills with an interest in medicinal chemistry, chemical biology, and interdisciplinary research. Candidates with prior experience in synthetic organic chemistry and\/or chemical biology are desired for this project. Additionally, the applicants should meet the eligibility criteria for entry into a PhD program at Curtin University.\u00a0<\/p>\n\n\n\n

    This project is open to Domestic applicants only.\u00a0<\/p>\n\n\n\n


    Scholarship\u00a0\u00a0<\/p>\n\n\n\n

    If you are identified as the preferred candidate for this project, you may be considered for an RTP scholarship<\/a>. <\/p>\n\n\n\n


    Enquires and How to Apply\u00a0<\/p>\n\n\n\n

    For enquires about this opportunity contact Dr Lisa Alcock at\u00a0Lisa.Alcock@curtin.edu.au<\/a><\/p>\n\n\n\n

    To formally apply submit an\u00a0Expression of Interest<\/a>\u00a0to Dr Lisa Alcock during the Central Scholarship round (July 1st – July 31st 2026)\u00a0<\/p>\n<\/div>\n","protected":false},"author":125,"featured_media":0,"template":"","faculties":[51],"hdr_types":[5487],"research_areas":[37,47],"class_list":["post-145572","hdr-r-projects","type-hdr-r-projects","status-publish","hentry","faculties-science-and-engineering","hdr_types-rtp-scholarship","research_areas-biomedical-and-clinical-science","research_areas-chemical-science"],"acf":false,"featured_image":false,"_links":{"self":[{"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/hdr-r-projects\/145572","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/hdr-r-projects"}],"about":[{"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/types\/hdr-r-projects"}],"author":[{"embeddable":true,"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/users\/125"}],"version-history":[{"count":0,"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/hdr-r-projects\/145572\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/media?parent=145572"}],"wp:term":[{"taxonomy":"faculties","embeddable":true,"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/faculties?post=145572"},{"taxonomy":"hdr_types","embeddable":true,"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/hdr_types?post=145572"},{"taxonomy":"research_areas","embeddable":true,"href":"https:\/\/www.curtin.edu.au\/research\/wp-json\/wp\/v2\/research_areas?post=145572"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}