{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T01:06:06Z","timestamp":1780362366927,"version":"3.54.1"},"reference-count":59,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research Fund UK","doi-asserted-by":"publisher","award":["C15532\/A21624"],"award-info":[{"award-number":["C15532\/A21624"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research Fund UK","doi-asserted-by":"publisher","award":["C16420\/A18066"],"award-info":[{"award-number":["C16420\/A18066"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A20FMDV2 is a 20-mer peptide that exhibits high selectivity and affinity for the tumour-related \u03b1v\u03b26 integrin that can compete with extracellular ligands for the crucial RGD binding site, playing a role as a promising \u03b1v\u03b26-specific inhibitor for anti-cancer therapies. Unfortunately, the clinical value of A20FMDV2 is limited by its poor half-life in blood caused by rapid renal excretion and its reported high susceptibility to serum proteases. The incorporation of poly (ethylene glycol) chains, coined PEGylation, is a well-established approach to improve the pharmacokinetic properties of drug molecules. Here, we report a systematic study on the incorporation of a varying number of ethylene glycol units (1\u201320) into the A20FMDV2 peptide to establish the effects of PEGylation size on the peptide stability in both rat serum and human plasma. In addition, the effect of acetyl and propionyl PEGylation handles on peptide stability is also described. Selected peptide analogues were assessed for integrin-\u03b1v\u03b26-targeted binding, showing good specificity and activity in vitro. Stability studies in rat serum established that all of the PEGylated peptides displayed good stability, and an A20FMDV2 peptide containing twenty ethylene glycol units (PEG20) was the most stable. Surprisingly, the stability testing in human plasma identified shorter PEGs (PEG2 and PEG5) as more resistant to degradation than longer PEGs, a trend which was also observed with affinity binding to integrin \u03b1v\u03b26.<\/jats:p>","DOI":"10.3390\/molecules27144331","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T05:41:06Z","timestamp":1657086066000},"page":"4331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synthesis and Systematic Study on the Effect of Different PEG Units on Stability of PEGylated, Integrin-\u03b1v\u03b26-Specific A20FMDV2 Analogues in Rat Serum and Human Plasma"],"prefix":"10.3390","volume":"27","author":[{"given":"Kuo-yuan","family":"Hung","sequence":"first","affiliation":[{"name":"The School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland 1010, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0009-5869","authenticated-orcid":false,"given":"Renata","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"The School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland 1010, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Desai","sequence":"additional","affiliation":[{"name":"Centre for Tumour Biology, Barts Cancer Institute-Cancer Research UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7086-4096","authenticated-orcid":false,"given":"Margaret A.","family":"Brimble","sequence":"additional","affiliation":[{"name":"The School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland 1010, New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand"},{"name":"The School of Biological Sciences, University of Auckland, 3A Symonds St, Auckland 1010, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Centre for Tumour Biology, Barts Cancer Institute-Cancer Research UK Centre of Excellence, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W. R.","family":"Harris","sequence":"additional","affiliation":[{"name":"The School of Chemical Sciences, University of Auckland, 23 Symonds St, Auckland 1010, New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Private Bag 92019, Auckland 1010, New Zealand"},{"name":"The School of Biological Sciences, University of Auckland, 3A Symonds St, Auckland 1010, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1177\/41.10.8245410","article-title":"Restricted Distribution of Integrin Beta 6 MRNA in Primate Epithelial Tissues","volume":"41","author":"Breuss","year":"1993","journal-title":"J. Histochem. 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