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A vascular endothelial growth factor (VEGF) binding peptide and a peptide against the protective antigen (PA) protein of<jats:italic>Bacillus anthracis<\/jats:italic>discovered through phage and bacterial display panning technologies, respectively, were modified with click handles and subjected to iterative<jats:italic>in situ<\/jats:italic>click chemistry screens using synthetic peptide libraries. Each azide\u2010alkyne cycloaddition iteration, promoted by the respective target proteins, yielded improvements in metrics for the application of interest. The anti\u2010VEGF PCC was explored as a stable<jats:italic>in vivo<\/jats:italic>imaging probe. It exhibited excellent stability against proteases and a mean elimination<jats:italic>in vivo<\/jats:italic>half\u2010life (<jats:italic>T<\/jats:italic><jats:sub>1\/2<\/jats:sub>) of 36 min. Intraperitoneal injection of the reagent results in slow clearance from the peritoneal cavity and kidney retention at extended times, while intravenous injection translates to rapid renal clearance. The ligand competed with the commercial antibody for binding to VEGF<jats:italic>in vivo<\/jats:italic>. The anti\u2010PA ligand was developed for detection assays that perform in demanding physical environments. The matured anti\u2010PA PCC exhibited no solution aggregation, no fragmentation when heated to 100\u00b0C, and \u2009&gt;\u200981% binding activity for PA after heating at 90\u00b0C for 1 h. We discuss the potential of the PCC agent screening process for the discovery and enrichment of next generation antibody alternatives.<\/jats:p>","DOI":"10.1002\/bip.22934","type":"journal-article","created":{"date-parts":[[2016,8,19]],"date-time":"2016-08-19T09:03:23Z","timestamp":1471597403000},"source":"Crossref","is-referenced-by-count":19,"title":["Protein catalyzed capture agents with tailored performance for<i>in vitro<\/i>and<i>in vivo<\/i>applications"],"prefix":"10.1002","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9305-3846","authenticated-orcid":false,"given":"Matthew B.","family":"Coppock","sequence":"first","affiliation":[{"name":"Sensors and Electron Devices Directorate U.S. Army Research Laboratory Adelphi MD 20783"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Candice R.","family":"Warner","sequence":"additional","affiliation":[{"name":"Excet, Springfield VA 22151 supporting USA Edgewood Chemical Biological Center Aberdeen Proving 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